Paulo H. G. Zarbin,* José A. F. P. Villar and Arlene G. Corrêa 2007 review.pdf · Nesta revisão...

J. Braz. Chem. Soc., Vol. 18, No. 6, 1100-1124, 2007.Printed in Brazil - ©2007 Sociedade Brasileira de Química0103 - 5053 $6.00+0.00

Rev

iew

*e-mail: [email protected]#This paper is dedicated to Prof. J. Tércio B. Ferreira, on the occasion ofthe 10th year of his decease.

Insect Pheromone Synthesis in Brazil: an Overview#

Paulo H. G. Zarbin,a,* José A. F. P. Villara and Arlene G. Corrêab

aDepartamento de Química, Universidade Federal do Paraná, CP 19081, 81531-990 Curitiba-PR, BrazilbDepartamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos-SP, Brazil

Nesta revisão estão descritas as sínteses de feromônios de insetos desenvolvidas e publicadaspor grupos de pesquisa brasileiros, e tem por objetivo apresentar o estado da arte desta área depesquisa no país e fornecer uma informação rápida sobre as moléculas já sintetizadas emetodologias empregadas. As sínteses estão apresentadas em ordem cronológica, exceto quandose trata de diferentes metodologias para a mesma molécula.

This review describes the syntheses of insect pheromones developed and published byBrazilian research groups and aims to present the state of the art of this area in the country, andalso to serves as a quick view of the already synthesized molecules and employed methodology.The syntheses are presented in chronological order, except when they refer to different approachesfor the same molecule.

Keywords. Brazil, chemical ecology, insect pheromone, organic synthesis

1. Introduction

The ever-increasing use of conventional pesticidesleads to resistant pests, severely alters natural ecology,damages the environment and, ultimately, affects theeconomy adversely. The number of insect and otherspecies developing resistance to pesticides is growingsteadily, forcing chemical companies to develop novelpesticide formulas. In response to the problems causedby the increased use of conventional pesticides, theconcept of integrated pest management (IPM) wasdeveloped. IPM combines chemical, biological andagrotechnical approaches to achieve pest control at areasonable cost while minimizing damage to theenvironment. The first step in IPM is effective monitoringby the use of pheromones.1

Pheromones are substances which occur in Nature andare used for chemical communication between animals. Theterm pheromone (from the Greek pherein = to transfer andhormon = to excite), coined by Karlson and Luscher,2 is asubstance which is secreted by an individual and receivedby a second individual of the same species, in which it releasesa specific reaction, for example, a specific behaviour or a

development process. The main ways of exploitingpheromones in pest control are: monitoring, mating disruptionand mass trapping.3 Such pheromone applications providesignificant cost reduction and environmental benefits to thefarmer, to the consumer and to the society.

The first chemical identification of a pheromone tookplace in the late 1950s, after almost two decades of work bya team led by Butenandt.4 The team chose to study thedomesticated silk moth, Bombyx mori, which could be rearedin the enormous numbers needed. The silk moth pheromonewas identified as (10E,12Z)-hexadecadien-1-ol (1),bombykol. This first sex pheromone identified was achiral,but in the late 1960s a number of chiral pheromones werediscovered such as (+)-exo-brevicomin 2, the pheromone ofthe western pine beetle, Dendroctonus brevicomis5 and (Z)-(-)-14-methylhexadec-8-en-1-ol (3), the sex attractant offemale dermestid beetle, Trogoderma inclusum6 (Figure 1).

An understanding of the relationship between structureand biological effect requires that the absolute

Figure 1. Structures of insect pheromones

OH

OH

1

O

O

2

3

1101Zarbin et al.Vol. 18, No. 6, 2007

configurations of the naturally occurring chiral pheromonesare determined. It is now well established that pheromonesare not always enantiomerically pure. Therefore, theirenantiomeric composition must be determined in detail.7

Difficulties are often encountered in stereochemicalstudies of pheromones, because they are usually obtainedin small quantities. Thus, organic synthesis plays anessential role on the pheromone chemistry, as it providesmaterial for rigorous determination of the (absolute)configuration of the molecules and for carrying outextensive biological tests. The synthesis of compound 3described in 1973 by Mori was the first successfulidentification of the absolute configuration of an insectpheromone by its enantioselective synthesis.8,9 Severalreviews have been described focusing on many aspects ofpheromone science.10-17

Rapid progress has been made in research on insectpheromones in Brazil during the last decade, includingthe identification, synthesis, biosynthesis and fieldevaluation of the bioactive compounds and continuingattempts are expected in the coming years.18 The growthof the field in Brazil naturally led to the organization ofnational meetings in the area. In December, 1999 the firstBrazilian Meeting on Chemical Ecology (I EBEQ) washeld at the Chemistry Department of Universidade Federaldo Paraná and nowadays the community looks forwardthe fifth issue of the meeting, scheduled for October, 2007.As a consequence of the large diffusion of research resultspresented at I EBEQ, a special issue of the Journal of theBrazilian Chemical Society (2000,11(6)) was dedicatedto Chemical Ecology. This issue features contributionsfrom research groups from Brazil and abroad and providesan overview of the area in the late 1990s.

In this review, we summarize insect pheromonesynthesis research in Brazil. The aim is to present thestate of the art of this area in the country, and also toserve as an overview of the already synthesized moleculesand employed methodology. The syntheses are presented

in chronological order, except when they refer to differentapproaches for the same molecule.

2. Synthesis of the pheromones

2.1. (E)- and (Z)-3,3-Dimethyl-Δ1,β-cyclohexaneethanal(4) and (Z)-3,3-dimethyl-Δ1,β-cyclohexaneethanol (5)

Compounds Z- and E-4 and 5 are components of thepheromone produced by male boll weevil, Anthonomusgrandis, and were identified and first synthesized byTumlinson et al.19 In 1978, Souza and Gonçalves describedthe syntheses of these components, being the firstpheromone synthesis developed in Brazil.20 The Z- andE-aldehydes 4 were prepared from commercially available3-methyl-2-cyclohexen-1-one, in 69% overall yield. Thethird component, the Z alcohol 5 was prepared byreduction of a mixture of aldehydes 4 with NaBH

4, in

quantitative yield (Scheme 1).

2.2. 7-Hydroxy-4,6-dimethyl-3-nonanone (6) (Serricornin)

Serricornin is the sex pheromone produced by femalecigarette beetle, Lasioderma serricorne.21-24 Its absoluteconfiguration was definitively established by Mori andco-workers25,26 as (4S, 6S, 7S)-6. Pilli and Murta27,28

described an efficient 12 step diastereoselective synthesisof (±)-6, in 12% overall yield (Scheme 2).

Ferreira et al. described a formal and enantioselectivesynthesis of (4S,6S,7S)-(-)-serricornin (6).29 The (4S,5S)-4-methyl-5-ethyl-δ-valerolactone was synthesized with ahigh degree of enantioselectivity (> 99% e.e.), startingfrom (R)-(+)-(E)-1-propenyl-p-tolylsulfoxide, having theenantioselective Marino’s lactonization as the key step(Scheme 3).

Two other approaches to the synthesis of (-)-6 werealso reported by Pilli and co-workers. In the first31 theoxazolidinone A was straightforwardly converted to the

O O

MeMgI/CuCl

orMe2CuLi

EtO OEt EtO

OEtEtO

HC(OEt)3

EtOH/

OEt

ZnCl2

CHOOHC

+NaOAc

AcOH/H2O/Δ

NaBH4, EtOH,

(quant. yield)

CH2OHHOH2C

+

(Z) - 4(E) - 4 (Z) - 5(E) - 5

69% overall yield

O O

MeMgI/CuCl

orMe2CuLi

EtO OEt EtO

OEtEtO

HC(OEt)3

EtOH/p-TsOH

OEt

ZnCl2

CHOOHC

+NaOAc

AcOH/H2O/Δ

NaBH4, EtOH,

(quant. yield)

CH2OHHOH2C

+

(Z) - 4(E) - 4 (Z) - 5(E) - 5

69% overall yield

Scheme 1.

1102 Insect Pheromone Synthesis in Brazil: an Overview J. Braz. Chem. Soc.

homochiral lactone B in 6 steps, a known32 precursor of (-)-6 (Scheme 4). In the second method,33 a short preparationof enantiomerically enriched (80% e.e.) (-)-6 wasdeveloped in 8 steps and 13% overall yield, from methyl(R)-3-hydroxypentanoate readily prepared by baker´s yeastreduction of methyl 3-oxopentanoate in the presence ofallyl alcohol as enzyme inhibitor (Scheme 5).

2.3. 1,7-Dimethylnonyl propanoate (7)

The sex pheromone emitted by female western cornrootworms, Diabrotica virgifera virgifera, was isolated andidentified as 1,7-dimethylnonyl propanoate (7).34 Thiscompound is also attractive to several Diabrotica species.35,36

Males of D. virgifera virgifera and D. virgifera zeaeresponded to (2R,8R)- and (2S,8R)-7, while D. porracearesponded exclusively to (2S, 8R)-7. Only the (2R, 8R)-7was attractive to the northern corn rootworm, D. barberi.The synthesis of (2S,8S)- and (2S,8R)-7 was described byFerreira and Simonelli,37 employing (S)-4-iodo-2-butanol Aas a key intermediate. The synthesis was accomplished usingremote stereochemical relationships between carbons 3 and9 of the 3,9-dimethyl decanolides B and C (Scheme 6).

2.4. 5-Hydroxy-4-methyl-3-heptanone (8) (Sitophilure)

In 1984, Phillips and co-workers38,39 identified the male-produced aggregation pheromone of the rice weevil,

Scheme 2.

OSiMe3

Oi) LDA, THF, -78 °C

ii) CH3CH2CHO

iii) NH4Cl (aq), 82%

OSiMe3

OOH Ac2O, CH2Cl2

Et3N, DMAP(cat),

98%

OSiMe3

OO

O

1) CH3CO2H (aq)

2) NaBH4, EtOH

3) NaIO4, EtOH, H2O

76% overall

OO

O

H

(C2H5O)3PCH(CH3)CO2C2H5

O

C6H6, NaH, 61%

O

O

CO2C2H5

1) H2, PtO2,

2) KOH, MeOH,

3) H3O+,

65% overall

O

O

C2H5MgBr

Et2O, -78 °C

OH O

(±) - 6 12% overall yield

Scheme 3.

S

O

Tol

1) (i) LDA, THF, HMPA, -78 °°

°

°

°

°

C

(ii) EtI -78 C, 63%

2) Cl3CCOCl, Zn(Cu), THF, - 40 C, 96%

3) Al(Hg), THF, MeOH, H2O, r.t. 84%

O

O

STol

1) RaNi, EtOH, 0 C, 66%

2) LiAlH4 , Et2O, 0 C, r.t., 98%

OH

OH 1) (i) p-TsCl, Py, CHCl3, O C

(ii) NaCN, DMSO, NaI, 90-95°C 67%

2) KOH, EtOH, H2 O, reflux

H3 O+ then benzene, , 89%

O

O

Ref. 30OHO

(-) - 6

20% overall yield; >99% e.e.

p-TsOH

Scheme 4.

N

O

O

O

Ph

1) (n-C4H9)2BOTf

2) C2H5CHO

3) H2O2, H2O, MeOH

80%

N

O

O

O

Ph

OH

LiOH, H2O2

89%OH

OOH

OTs

O

O

1) LiAlH4

2) p-TsCl, Et3N

3) Ac2O, Et3N

52%

Ref. 32 OHO

(-) - 6

O

O

1) t-BuOK

2) LDA, MeI48%

A

B


Sitophilus oryzae, and of the maize weevil, Sitophiluszeamais, as 5-hydroxy-4-methyl-3-heptanone (8) and namedthis new compound as sitophilure. The syntheses of thefour possible stereoisomers of 8, followed by laboratorybioassays, revealed the (4S,5R)-8 as the active isomer.40,41

Pilli et al.42 described the synthesis of racemic 8employing the addition of the lithium enolate of 2-methyl-2-trimethylsilyloxy-3-pentanone to propionaldehyde,followed by ethyllithium addition and oxidative cleavagewith periodic acid (16.5% overall yield). In the same work,the addition of the boron enolate of 3-pentanone topropionaldehyde, followed by oxidative treatment,afforded a 9:1 mixture of (4SR, 5RS)- and (4SR, 5SR)-8,in 43% overall yield (Scheme 7).

Pilli and Riatto43 described later an asymmetricsynthesis of (+)-sitophilure (8). The synthesis was carried

out in 12 steps, in 18% overall yield and 82%enantiomeric excess, with the enzymatic reduction ofmethyl 3-oxopentanoate with S. cerevisiae in thepresence of ethyl chloroacetate being used to generatethe key chiral synthon (Scheme 8).

2.5. 3,5-Dimethyl-6-(l’-methylbutyl)-tetrahydro-2H-pyran-2-one (9) (Invictolide)

Invictolide is a component of the queen recognitionpheromone of the fire ant Solenopsis invicta44,45 Theabsolute configuration of the natural product wasestablished as (3R,5R,6S,l’R)-9, after the development ofthe synthesis by Mori and Nakazono.46

A stereoselective total synthesis of (±)-invictolide(9) was described by Pilli and Murta.47 The TiCl

4-

Scheme 5.

O

O OBaker´syeastAllyl alcohol80% e.e., 88%

O

OH O

i) LDA, THF, -78 °C

ii) MeI, DMPU O

OH O

1) LiAlH4, THF, r.t.

2) p-TsCl, Et3N, CH2Cl2,

DMAP cat.

OTs

OH1)p-NO2C6H4CO2H, Ph3P,

DEAD, C6H6, r.t., 76%

2) K2CO3, MeOH, H2O, 93%

3) (CH3CH2CO)2O, Et3N,

CH2Cl2, DMAP (cat.), 82%

OTs

OCOCH2CH3

t-BuOK, THF

0 °C, 55%

O

O

EtMgBr, Et2O, -78 °C 70%

OHO

(-) - 6

13% overall yield; 80% e.e.

Scheme 6.

OEt

O O1) Baker's yeast, 82%, 85% e.e.

2) LiAlH4, Et2O, 5 h, 82% OH

H OH 1) p-TsCl, Py, 84%

2) NaI, Acetone, 79% I

H OH

A

OSiMe3

OSiMe3 OLi

OLi

HMPA/THF

(1:1), A, 60%

MeLi/DME

O

OH

OH

1) Pb(OAc)4, C6H6, 94%

2) HS(CH 2)2SH, CH2Cl2,

BF3.Et2O, 95%

O

O

S S

1) Ra (Ni), 92%

2) LDA, THF,PhSeCl, H2O2, 78%

O

O

CuI/Et2O, MeLi

BF3.Et2O, -70 °C, 74%O

O

O

O

O

O

1) LDA, THF, PhSeCl,H2O2, 82%

2) H2, Rh/C, MeOH, 97%

1) LiAlH4, THF, 96%

2) p-TsCl, Py, 85%3) LiB(C2H5)3H, THF, 76%

4) CH3CH2COCl/Py, 81%

1) LiAlH4, THF, 96%

2) p-TsCl, Py, 100%3) LiB(C2H5)3H, THF, 75%

4) CH3CH2COCl/Py, 80%

O

O

(2S,8S) - 7

(2S,8R) - 7

B

C

6.4% overall yield

5.8% overall yield


mediated addition of sylil ketene thioacetal to (±)-3-(benzyloxy)-2-methylpropionaldehyde affordedexclusively a thioester, which was straightforwardlyconverted to diol A (ca. 31% yield). The same diol wasalso prepared after LiAlH

4 reduction of the major aldol

formed in the condensation between the lithium enolateof 2,6-di-ter-butyl-4-methylphenyl propanoate and (±)-2-methylvaleraldehyde. Intramolecular alkylation (t-BuOK, THF) of B or C gave a 40:60 mixture of (±)-9and its C(3) epimer (10 steps, 8% overall yield).Catalytic hydrogenation of unsaturated lactone Dafforded (±)-9 in 80% yield (8 steps, 14% overall yield).(Scheme 9).

2.6. (E)-6-Nonen-1-ol (10) and methyl (E)-6-nonenoate(11)

Mahajan and Tresvenzol48 have prepared (E)-6-nonen-1-ol (10) and methyl (E)-6-nonenoate (11), two componentsof the sex pheromone of the Mediterranean fruit fly, Ceratitiscapitata50, starting from cyclohexanone (Scheme 10).

2.7. (Z)-4-(1’, 5’-dimethyl 1’, 4’-hexadienyl)-1, 2-epoxy-1-methylcyclohexane (12)

Compound 12 is the male-produced sex pheromone of thegreen stink bug, Nezara viridula,51 an important pest of severalagricultural crops that is distributed throughout many parts ofthe world.52 The Brazilian population of N. viridula employs(Z)-(1S,2R,4S)-12 as its pheromone.53 Baptistella and Aleixo54

described the synthesis of pheromone 12 by a convergentstereocontrolled sequence, using (S)-(-)-perillyl alcohol asstarting material (18% overall yield, 99% e.e.) (Scheme 11).

2.8. (Z)-9-Tricosene (13)

Carlson and co-workers described the identificationof the sex pheromone produced by female house fly,Musca domestica as (Z)-9-tricosene (13).55 Marques et al.reported the synthesis of 13 employing a Kolbe electrolysisof the oleic and heptanoic acids, in MeOH/MeONa in28% overall yield (Scheme 12).56

Scheme 8.

OMe

O O

OMe

OH OBaker’s yeast(YSC-1),

ClAcOEt,70%, 82% e.e.

1) (i) LDA, THF, -78 °C(ii) MeI, DMPU;

OTBS

OH

2) LiAlH4, THF, r.t.

3) TBSCl, Et3N,CH2Cl2,

DMAP(cat.), r.t.(89% yield, 3 steps)

1) p-NO2C6H4CO2H, Ph3P,

DEAD, C6H6, r.t.

2) K2CO3, MeOH,

H2O, r.t.

(80% yield, 2 steps)

OTBS

OH 1) TBSOTf, 2,6-lutidine,CH2Cl2, 0 °C, 94%

2) HF-Py, THF, r.t., 83%OH

OTBS

1) Swern oxid.

2) EtMgBr, Et2O

(79% yield, 2 steps)

OTBS OH

2) TBAF, THF, r.t.(60% yield, 2 steps).

OH O

(+) - 8

18% overall yield; 82% e.e.

1) Swern oxid.

Scheme 7.

OSiMe3

Oi) LDA, THF, -78°

°

°

C

ii) CH3CH2CHO, 82%

OSiMe3

OOH C2H5OC2H3, CH2Cl2

PPTS, CH2Cl2, 98%

OSiMe3

OOEE OOH

i) C2H5Li, Et2O, -30 C

ii) H5IO6, MeOH, r.t. 28%

OOHO

Bu2BOTF, Et2O, i-PrNEt, -78 C,

CH3CH2CHO, then 30% H2O2,

MeOH

(±) - 8

(±) - 8

16.5% overall yield

43% overall yield


2.9. cis-2-Isopropenyl-1-methylcyclobutaneethanol (14)(Grandisol)

Grandisol (14) is the major component of the male-produced pheromone of the cotton boll weevil,

Anthonomus grandis.19 The alcohol and its correspondingaldehyde, grandisal, were also found in the pheromonalsecretion of several other beetles.57 The potential use ofthis pheromone in traps for monitoring crop infestationin integrated pest management prompted research groups

Scheme 9.

StBu

OSiMe2tBu

+ Ph O H

O

TiCl4, CH2Cl265%

Ph O

OH O

StBu

5 Steps

HO

OH

tBu

tBu

O

O

(i) LDA, THF, -78 °C(ii) (±)-2-methylvaleraldehyde

ArO

O OH

A

2 Steps

X

O

O

1) (i) p-T sCl, CH2Cl2, Et3N, -15 °C,

(ii) (CH3CH2CO)2O, CH2Cl2, Et3N,

DMAP (cat.), r.t. (92% overall yield)

2) NaI, acetone, reflux, 73%B : X = OTs

C : X = I

O

O

H

4 Steps

D

H2, EtOH, Pd/C, 80%

O

O

H

(±) - 9

t-BuOK, THF, 0 °C, 75-78%

O

O

H

A

8 steps (14% overall yield)

B C

10 steps (8% overall yield)

(±) - 9 (60:40)

Scheme 10.

O O

O

Acylation

Ref. 49O

OCl

NaClO, H+, EtOAc, 96%

or SO2Cl2, CCl4, 91%

Acetone, MeOH,

K2CO3, reflux, 60%

CO2Me

OCl

TosNHNH2, AcOH,

CH2Cl2, KOAc, 20% CO2Me

CO2Me

OMsCl

1) NaBH4, MeOH, 95%

2) MsCl, Et3N, CH2Cl293%

NaI, DMSO, Δ, 45%

CO2Me

(E) - 11

CO2Me+

(Z) - 11

Pd/C Lindlar, H2, Quinoline,

quant.

OH

Ref. 49 and 50

(E) - 10

(3)

(Z) - 11

E/Z 8:2

12% overall yield

23% overall yield95%


world wide to search for an efficient preparation of themore active (+)-enantiomer.

Monteiro and Zukerman-Schpector58 reported a 10steps synthesis of (1S,2R)-2-acetyl-1-methylcyclo-butaneacetic acid A (11% overall yield, > 99% e.e.),in which the key step was a rhodium catalyzedintramolecular carbenoid cyclization of an α-diazo-β-ketosulfone, readily available from (+)-citronellol.Because A has already been converted into

(+)-grandisol (14),59,60 the described preparationconstitutes a formal synthesis of the optically activepheromone (Scheme 13).

Monteiro and Stefani61 described a stereoselectivesynthesis of (±)-grandisol (14) in 19% overall yield,starting with a simple cyclobutyl derivative to whichthe methyl group and the 1,2-cis disposed side chainswere appended through a remote alkylation protocol(Scheme 14).

Scheme 11.

OH OH

O1) MsCl, Py, 99%

2) LiAlH4, Et2O, 70%

3) KMnO4,CH2Cl2,

dibenzo-18-crown-6, 73%

O

O 1) n-BuLi, THF,Ph2PO(CH2)2CH=C(CH3)2, 57%

2) NaH, THF, 66%

O

(Z)-(1S,2R,4S)-12

Diethyl D-(-)-tartrate,

Ti(Oi-Pr)4, tBuOOH,

CH2Cl2, 93%

OH

O

+

94 : 6


Scheme 12.

CH3(CH2)7 (CH2)7CO2H CO2H+Kolbe electrolysis

CH3ONa, CH3OH

CH3(CH2)7 (CH2)12CH3

(Z) - 13 28% overall yield

Scheme 13.

OH

1) (i) NaH, MeI, DME, reflux(ii) CrO3, OsO4, Me2CO

(iii) MeOH, H+, CH2Cl2, reflux, 81%

2) PhSO2CH2Na, THF/DMSO, r.t., 92%

PhO2S

OMe

O1) 2-Chloro-1-ethyIpyridinium

fluoroborate, NaN3, NaOAc,

MeOH, r.t.

2) Rh2(OAc)4 , C6H6, 35 - 40 °C

SO2PhO

OMe

1) NaI, Me3SiCl, MeCN, reflux, 71%

2) NaH, THF, r.t. 94%3) MeMgI, THF/Et2O, r.t. 94%

HOSO2Ph

(i) SOCl2, Py, CH2CI2, r.t.

(ii) t- BuOK, DMSO, r.t. 96%

SO2Ph SO2Ph

(ii)

+

1) 30% H2O2, HCO2H, 100 °C,

then NaOH, MeOH, r.t. 73%

2) Na/Hg, MeOH, r.t. 66%3) NalO4, RuCl3, H2O, r.t. 83%

O

OHO

A

HO

(+) - 14

Ref. 59 and 60

>99 e.e.

11% overall yield; >99% e.e

2.10. Methyl 2,6,10-trimethyldodecanoate (15) and methyl2,6,10-trimethyltridecanoate (16)

In 1994, Aldrich and co-workers identified methyl2,6,10-trimethyldodecanoate (15) and methyl 2,6,10-trimethyltridecanoate (16) as components of the male-produced sex pheromones of the stink bugs, Euschistusheros and Euschistus obscurus.62,63 The same compoundswere later found in headspace volatiles from Brazilian

male bug, Piezodorus guildinii, but the biological rolesof these compounds in the species have not beendelineated.64,65 A stereospecific synthesis of the eightstereoisomers of 16 was developed by Mori and Murata,66

but the absolute configuration of this insect-producedcompound was never reported.

Ferreira and Zarbin67 described enantioselectivesyntheses of the stereoisomers (2R,6S,10S)- and(2S,6S,10S)-15, out of eight possible, employing the

Scheme 14.

SO2PhPhO2S

O

SO2Phi) MeLi, THF, -15 °C

ii) 2-(phenylsulfanylmethyl)oxiraneiii) H2O2, HOAc

iv) Jones Reagent, r.t. 87%

1) NaOH, MeOH, r.t., 97%

2)AlMe3, CuBr, THF, 0 °C, 80%

O

SO2Ph

N2

SO2Ph

O

1) i) NaOH, MeOH, reflux

ii) H+, 96%

2) Me2S.BH3, 95%

3) i) MeLi, THF, -15 °Cii) (M eS)2

iii) H2O2, HOAc, 88%

i) t-BuMeSiCl, Et3N,

DMAP, CH2Cl2, r.t.

ii) NaOH, MeI, BTEAC, C6H6/H2O

iii) Dowex 50X8, MeOH, r.t., 78%

MeLi, THF, 0 °C, 56.6%

(±) - 14

HO

SO2MePhO2S

HO

PhO2S

HO

SO2Me1) 2-Chloro-1-ethylpyridinium

tetrafluoroborate, NaN3,

NaOAc, MeOH, 0 °C

2) Rh2(OAc)4, CH2Cl2, reflux

19% overall yield

Scheme 15.

OH

i) B2H6

ii) H2O2, NaOH,

THF, 0 °C, 93%OH

OHH

(-)- isopulegolor

(+)- neo-isopulegol

80% Hβ20% Hα

from (-)- isopulegol

70% Hβ30% Hα

from (+)- neo-isopulegol

1) separation of diastereoisomers, 76.4%2) NaH, BnBr, THF, -5 °C, 70%

3) PCC, CH2CI2, r.t., 93%

4) m-CPBA/NaHCO3, CH2Cl2, r.t. 90%

OO

OBn

H

H

O

OBn

6 steps OMe

O

(2R,6S,10S)-15, from ( -)- isopulegol

OMe

O

(2S,6S,10S)-15, from (+)- neo-isopulegol

PCC, CH2Cl2, r.t., 90%OH

OBn

or


1) MeOH, H2SO4 (cat.),

reflux, quant.

2) p-TsCl, Py, CHCl3,

0 °C, 70%

3) LiAlH4, Et2O, r.t., 60%


stereoselective hydroboration of (-)-isopulegol and (+)-neo-isopulegol as the key reaction, and incorporating athird chiral synthon, (S)-(+)-1-bromo-2-methylbutane (3%overall yield, >99% e.e.) (Scheme 15). In theory, thissynthesis can be modified to produce any of the otherisomers by an appropriate combination of the otherenantiomers of these three synthons.68

A nonselective synthesis of 15 and 16 described byZarbin et al.69 involved chain extension of the tosylate of(±)-citronellol with 2-methylpentyl or 2-methylbutylmagnesium bromide to give the appropriate carbonskeleton. Allylic oxidation with SeO

2, hydrogenation and

adjustment of functional groups completed the synthesis

(8 and 16% overall yield, respectively) (Scheme 16).Zarbin et al.70 published another synthesis based oncitronellol, reversing the modification of the ends of thechain. After an allylic oxidation and two Wittig reactions,the pheromone 15 (12% overall yield) was obtained ingood yields (Scheme 17).

2.11. 1-Hydroxy-5-nonanone (17)

The hydroxy-ketone 17 was identified as a minorcomponent of the rectal glandular extract and volatileemission of males of the fruit fly Bactrocera cacuminatus.71

Ferreira and Zarbin72 described an expeditious synthesis of

Scheme 16.

RHO

R = MeR = Et

Ph3P /Br2,

CH2Cl2, 49 /73%

RBr

R = MeR = Et

R = H

R = Tsp-TsCl, Py, 75%

Mg, Et2O, Li2CuCl4

R = Me, 85%R = Et, 79%

1) SeO2 /t-BuOOH,

2) NaBH4 /MeOH

H2 /Pt2O

R = Me, 37%R = Et, 45%

R = Me, 88%R = Et, 99%

1) Jones oxid. /acetone

2) CH2N2, Et2O

15; R = Me, 75% (8% overall yield)

16; R = Et, 82% (16% overall yield)

OMe

R

O

R

ORR

OH

R

OH

Scheme 17.

OH

1) Ac2O, Py, 95%

2) SeO2 / t-BuOOH,

CH2Cl2, 40%

OAc

1) K2CO3, MeOH, 99%

2) Swern oxid.

H

O

1) HOCH2CH(CH3)CH2PPh3Br,

n-BuLi, THF

2) H2, Pd/C, 25 psi

OH1) Jones oxid.

2) CH2N2, Et2O

OMe

O

15

Ph3PCH3Br,

n-BuLi, THF, 57%OAc

O

H

12% overall yield


17 in four steps and 34% overall yield, starting fromcyclopentanone. The final product was obtained inequilibrium with the respective hemiacetal (Scheme 18).

2.12. (Z)-5-Decenyl acetate (18a), (Z)-8-dodecenyl acetate(18c), (E)-8-dodecenyl acetate (19c), decyl acetate (20),and hexadecyl acetate (21)

Mahajan and Resck73 described the synthesis of severalacyclic insect pheromones, along with their geometric and/or positional isomers, starting from Z-lactones, which areeasily available from the corresponding acetyleniclactones, prepared from cycloalkanones. The Z to E

isomerization of alkenyl acetates 18a-d to 19a-d wascarried out both by a catalytic technique (NaNO

2, HNO

3,

Δ) and chemical inversion procedure (NBS, TFA; NaI,DMF, Δ). Decyl acetate (20) and hexadecyl acetate (21),pheromone components of the turnip moth Agrotis segetumand the male butterfly Lycorea ceres ceres, respectively,were obtained by the catalytic hydrogenation of thecorresponding Z-alkenyl acetates (Scheme 19).

2.13. (3E,5Z)-3,5-Dodecadienyl acetate (22)

(3E,5Z)-3,5-Dodecadienyl acetate (22) was identifiedby Unelius et al. as the sex pheromone of the leafroller

Scheme 18.

O

BuMgBr

THF, 65%

HO Bu

/SiO2

CH2Cl2, 77%

Bu

i) O 3, MeOH

ii) NaBH4, MeOH, 91%

OH

OH

NaOCl

CH3COOH, 75%

O

OH17

O

OH

34% overall yield

p-TsOH

Scheme 19.

1) MeOH, MeONa, 20 - 24h

2) MsCl, Et3N, CH2Cl2, -15°C 3h

1) LiAlH4, Et2O,

-15 °C to reflux

2) Ac2O, Py(cat.), 80 - 90 °C

Lindlar, H2

OO

n

mO

O

n

m

18 a-d

1) NaNO2, HNO3, 70 - 75 °C, 1h

or 2) NBS, TFA, 0 °C, 30 min;

NaI, DMF, 90 °C, 20-22h 19 a-d

n m

CO2OAc

18b and 18d

Pd/C, H2

decyl Acetate (20) and hexadecyl acetate (21)

a) m = n = 1; b) m = 0, n = 2; c) m = 0, n = 4; d) m = 0, n = 8

n

m

CH2OAc

n

m OMs

CO2Me

Scheme 20.

CuBr.Me2SHexylMgBr (2 eq)

HH

THF, -78oC

Hex ) CuMgBr22

I

OH

TMEDA, -45oC to r.t., 52%

HexOH

1) LiAlH4/Diglyme/reflux;

NaOH 0.1 M

2) Ac2O/Py, 90%Hex OAc

22

46.8% overall yield


moth Bonagota cranaodes, an economically importantinsect pest of apples in Southern Brazil.74 Simonelli et al.75

described a stereoselective synthesis of this compound usingmethodology based on the coupling of a Z-alkenyl cupratewith 1-iodo-2-butyn-4-ol (46.8% overall yield) (Scheme 20).

2.14. 4,8-Dimethyldecanal (23)

In 1980, Suzuki identified 4,8-dimethyldecanal (23)as the aggregation pheromone of the red flour beetle,Tribolium castaneum, and of the confused beetle,Tribolium confusum, notorious pests of various storedfoodstuffs.76,77 Mori and co-workers78,79 established theabsolute configuration of the pheromone as (4R,8R)-23.Suzuki et al.80 later found that a mixture of the isomers(4R,8R)- and (4R,8S)-, in a ratio of 8:2, was about 10times more active than (4R,8R)-23 alone.

Zarbin et al.81,82 developed a stereospecific synthesisof all four possible isomers of 23. The synthesis wasachieved by connecting the chiral building blocks (R)-2-methyl-1-bromobutane, (R)-A, (derived from methyl(S)-3-hydroxy-2-methylpropionate),83,84 and (S)-2-methyl-1-bromobutane, (S)-A, commercially available,with (R)- and/or (S)-citronellol derivatives B (Scheme21).

2.15. 3,5,6-Trimethyltetrahydropyran-2H-one (24)

Brown and Moore85 reported the identification ofδ-lactone 24 in the extract of male heads of Calomyrmexsp. ants, that was presumed to function as a sexpheromone. Pilli et al.86 described the synthesis of fourracemates of lactone 24. The anti-hydroxy ester A was

produced through the stereoselective aldol condensationof the E-lithium enolate derived from 2,6-di-tert-butyl-4-methylphenyl propionate and acetaldehyde.Coumpoud A was converted into tosylate B, which wasemployed as commom intermediate in two differentroutes of the synthesis of δ-lactones 24a and 24b(Scheme 22). Similarly, a mixture of δ-lactones 24cand 24d was prepared starting with the stereoselectivealdol condensation of acetaldehyde and the lithiumenolate of the syn-selective silyloxyketone C (Scheme23). Based on the comparison of mass spectra and gaschromatographic properties of lactones 24a-24d withthose reported in the literature for the natural product,85

the relative configuration was assigned as(3SR,5RS,6SR)-24.

2.16. (E)-4-Oxo-2-hexenal (25)

In 2000, Zarbin et al.87 described the identification of(E)-4-oxo-2-hexenal (25) as component of the alarmpheromone system of Piezodorus guildinii, a member ofthe stinkbug complex in soybeans that is an economicallyimportant pest in Brazil.88 The same compound has beenfound in secretions from many other bug species.89 Toconfirm this identification, the authors synthesized(E)-25 in five steps and 22% overall yield, starting from(E)-1,4-butenediol87 (Scheme 24).

2.17. (2R,3R,7S)-3,7 -Dimethylpentadecan-2-ol (26)(Diprionol)

The pine sawfly, Neodiprion sertifer, is a widespreadand economically important forest insect in North

Scheme 21.

Br

(4R, 8R) - 23 (58% overall yield; 96% e.e.)

(4S, 8R) - 23 (66% e.e.)

O *O3, CH2Cl2,

DMS, 83%

*(R)-A , Mg, THF,

Li2CuCl4, 82%

(R)-A

BrPPh3, Br2,

CH2Cl2, 75%THPO

Ref. 83 and 84

HO OMe

O

O *

(R)-citronellol; 97% e.e.(S)-citronellol; 67% e.e.

*OH

(4R, 8S) - 23 (57% overall yield, 97% e.e.)

(4S, 8S) - 23 (67% e.e.)

O3, CH2Cl2,

DMS, 81%

(S)-A =

(S)-A Mg, THF

Li2CuCl4, 77%

p-TsCl, Py, 0oC

CHCl3, 86%

OTs*

*

B

B


America, Japan, and Europe.90 Anderbrandt et al.91 haveinvestigated the geographic pattern of male sawflyresponses at eight field sites ranging from Japan in theeast to Canada in the west. It has been demonstrated thatthe main sex pheromone components of this species are

the acetate or propionate of 3,7-dimethylpentadecan-2-ol(diprionol). Moreira and Corrêa92 described an enantio-selective synthesis (96.6% e.e.) of (2R,3R,7S)-diprionol(26) in 12 steps and 7.5% overall yield, starting fromcommercial (-)-isopulegol67(Scheme 25).

Scheme 22.

O

OtBu

tBu

i) LDA, THF, -78 °C

ii) CH3CHO, 60%

OOH

OBHT

1) LiAlH 4, THF, r.t. 70%

2) p-TsCl, Et3N, CH2Cl2,

DMAP(cat.), -15°C, 90%

OH

OTs

A

(EtCO)2O, Et3N,

CH2Cl2, r.t. 85%

t-BuOK, THF,-20° to 0°C, 50%.

O

OTs

O

O

O

O

O

+

24a 24b

3:2

B

BnBr, NaH,DMF, r.t. 60%

OBn

OTs

1) KOH, H2O, DMSO, 80-90°C, 60%

2) (COCl)2, DMSO, CH2Cl2, -78°C;

then Et3N, -78°C to r.t. 87%

3) (EtO)2P(O)CH(Me)CO2Et,

NaH, C6H6, 0°C, 70%

OBn O

OEt

1) H2, Pd/C, EtOH

2) , C6H6, r.t.

60% (two step)

O

O

O

O

24a 24b

2:1

16% overall yield

5% overall yield

+

B

p-TsOH

Scheme 23.

OSiMe3

Oi) LDA, THF, -78 °C

ii) CH3C HO, 90%

OSiMe3

OOH 1) Ac2O, Et3N, DMAP(cat.),

CH2Cl2, 85%

2) aq. HOAc, THF, 80%

OSiMe3

OOAc1) NaBH4, MeOH, 0°C, 90%

2) NaIO4, H2O, EtOH, 0°C, 78%

3) (EtO)2P(O)CH(Me)CO2Et,

NaH, C6H6, 0°C, 50%

OAc O

OEt

1) H2, Pd/C, EtOH, 95%

2) i)KOH, MeOH, reflux.ii) , C6H6, rt. 60%

O

O

O

O

24c 24d

1:4

12% overall yield

+

C

p-TsOH


2.18. 1-Ethylpropyl 2-methyl-3-hydroxypentanoate (27)(Sitophilate)

The male-produced aggregation pheromone of thegranary weevil, Sitophilus granarius, was identified byPhillips et al.93 as 1-ethylpropyl 2-methyl-3-hydroxy-pentanoate (27), sitophilate. Bioassays employing all ofthe synthetic isomers revealed (2S,3R)-27 to be the naturalpheromone.94

Mateus et al.95 described a diastereoselectivesynthesis of racemic 27, with a key step being adiastereoselective heterogeneous catalytic hydrogenationreaction of Baylis-Hillman adducts originating fromaliphatic aldehydes (Scheme 26).

2.19. N-2’-Methylbutyl-2-methylbuthylamide (28)

The four stereoisomers of N-2’methylbutyl-2-methylbutylamide (28), the sex pheromone of the longhorn

beetle Migdolus fryanus, an economically important pest ofsugarcane in South America,96 were synthesized bySantangelo et al.84 The key intermediate 2-methylbutan-1-olis commercially available only in its (S)-(-) form. The (R)-(+)-enantiomer was obtained optically pure from methyl (S)-(+)-3-hydroxy-2-methylpropionate, in five steps (Scheme 27).

2.20. (1S,5R,7S)-5-Ethyl-7-methyl-6,8-dioxabicyclo[3.2.1]octane (29) (exo-Isobrevicomin) and (1R,5S,7R)-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane (2) (exo-Brevicomin)

(-)-exo-Isobrevicomin (29) and (+)-exo-brevicomin (2)are volatile substances produced by males of the beetlesDendroctonus spp., which infest pine trees found in thenorthern hemisphere, frequently causing the death of theirhost.97-99 The isolation and the first synthesis of (-)-29,and the respective hydroxylated derivatives, were reportedin 1996 by Francke and co-workers.100

Scheme 25.

OH

(-)- isopulegol

p-TsCl, Py, 93%OTs

OBn

n-HexMgBr, Li2CuCl4

THF, -78 °C, 90%OBn

1) H2, Pd/C, MeOH, 73%

2) PCC, CH2Cl2, 81%

H

O

CH3MgBr, THF, -100 °C

69%, dr = 4:1

OH

(2R,3R,7S)-26

OH

OBn

see scheme 15

7.5% overall yield; 96.6% e.e

Scheme 24.

HOOH

DHP,

THF, 60%

HOOTHP

PCC/Al2O3

CH2Cl2, 80%

EtMgBr

THF, 65%

OTHP

OH

MeOH

, 88%

PCC/Al2O3

CH2Cl2, 80%

O

O

25

OOTHP

OH

OH

22% overall yield

p-TsOH

p-TsOH


In order to obtain these aggregation pheromones,which present the 6,8-dioxabicyclo[3.2.1]octane structure,the synthetic strategies utilized by Resck and Sousa101 hadas key steps the Sharpless asymmetric dihydroxylationand a conjugate addition reaction, promoted by Zn(Cu)couple in aqueous medium and accelerated by ultrasound.The conjugate addition of acetonides A and C to theunsaturated ketones, methyl vinyl ketone and ethyl vinylketone, respectively, furnished adducts B and D. Theintramolecular catalyzed cyclization of compounds B andD with phosphotungstic acid (H

3PW

12O

40) produced exo-

isobrevicomin 29 (17% overall yield) and exo-brevicomin2 (23% overall yield) (Scheme 28).

2.21. 2-Methyl-4-octanol (30)

2-Methyl-4-octanol (30) has been identified as acomponent of the aggregation pheromones of several

curculionid species.102-104 Baraldi et al.105 reported anenantioselective synthesis of (R)- and (S)-30. The (S)-isomer was efficiently prepared in five steps and 20%overall yield (99% e.e.), and its (R)-enantiomer in six stepsand 14% overall yield (99% e.e.), both from commercialisovaleryl chloride. The key step of this synthetic routewas the asymmetric reduction of ethyl 5-methyl-3-oxohexanoate with Saccharomyces cerevisiae to itscorresponding (S)-alcohol A in high enantiomeric excess(Scheme 29).

Recently, Zarbin et al.106 identified alcohol 30 as amale-produced aggregation pheromone of the sugarcaneweevil, Sphenophorus levis. The authors synthesizedboth enantiomers in five steps (15% overall yield) and92% e.e. from commercially available (R)- and (S)-2,2-dimethyl-1,3-dioxolane-4-methanol as startingmaterial. Enantiomeric resolution by gas chromato-graphy with a chiral column demonstrated that the

Scheme 26.

H

OO

OMeDABCO,

r.t., 8 days, 44%

+

O

OMe

OHTBSCl, DMF,

imidazole, r.t., 12h, 78%

O

OMe

OTBSH2, 5% Pd/C,

AcOEt, 82%

O

OMe

OTBS

+

O

OMe

OTBS

syn : anti100 : 0

1) LiOH, MeOH-H2O (3:1),

20h, r.t., 75%

2) 3-Pentanol, DMAP, DCC,

CH2Cl2, 4h, 0oC to r.t., 89%

3) HF, CH3CN, r.t., 1h, 80%

O

O

OH


Scheme 27.

HO OMe

O

H

1) DHP, , THF, 93%

2) LiAlH4, Et2O, 0-5 °C, 85%

3) p-TsCl, Py, 95%

THPO OTs

H

1) MeMgI, THF,

Li2CuCl4, -80 °C, 82%

2) Amberlyst 15, MeOH

H2N

H

(R)-B

Cl

H

O

1) NH3, 74%

2) LiAlH4, THF

(R)-A

N

O

H H

(R)-B, Py,

CH2Cl2, 76%N

O

H H

(S)-B (commercial)

Py, CH2Cl2, 72%

(2'R, 2R) - 28 (2'R, 2S) - 28

O

O O

HH

(S)-(commercial)

(R)-BN

O

H H

(2'S, 2R) - 28

(S)-BN

O

H H

(2'S 2S) - 28

Cl

H

O

(R)-A

1) Jones reag., 76%

2) SOCl2, 100%

HO

H

p-TsOH


natural alcohol possessed the (S)-configuration (Scheme30).

In order to establish the importance of thestereochemistry on the biological activity of thiscompound, Zarbin et al.107 described a new and highlyenantioselective approach to the synthesis of natural

(S)-30, starting from the easily available D-mannitol,in a route that employed the known (R)-glyceraldehydeacetonide as key intermediate. The GC analysis of anacetyl derivative of the final product, using a chiralstationary phase column, revealed an enantiomericexcess higher than 99.5% (Scheme 31).

Scheme 28.

HO

1) p-TsCl, KOH, Et2O,

-10 °C, 1.5 h, 80%

2) NaI, acetone, 25 °C,16 h, 95%

3) AD-mix-α, MeSO2NH2,

NaHCO3, t-BuOH:H2O (1:1),

0 °C, 15 h, 76%

I

OH

OH

EVK, Zn(Cu), EtOH:H2O (7:3),

ultrasound, 25 °C, 2 h, 30%

O OOH3PW12O24 cat.,

CH2Cl2, 25 °C, 4h, 96%

O

O

HO

1) p-TsCl, KOH, Et2O,

-10 °C, 1.5 h, 85%

2) NaI, acetone, 25 °C,16 h, 95%

3) AD-mix-β, MeSO2NH2,

NaHCO3, t-BuOH:H2O (1:1),

0 °C, 15 h, 80%

I

OH

OH

MVK, Zn(Cu), EtOH:H2O (7:3)

ultrasound, 25 °C, 2 h, 40%

H3PW12O24 cat.,

CH2Cl2, 25 °C, 4h, 95%

O

O

(+) - 2

(-) - 29

2,2-dimethoxy-propane,

PPTS, 25 °C, 5 h, 98%I

OO

A

2,2-dimethoxy-propane,

PPTS, 25 °C, 5 h, 99%

I

OO

B

C

D

O OO

17% overall yield

23% overall yield

Scheme 29.

Cl

O

LiCH2CO2Et

85%

O

CO2EtBaker's yeast

allyl alcohol50%, 99% e.e.

OH

CO2Et

(S) - A

OH

CO2Et

(R) - A

1) p-NO2C6H6CO2H

Ph3P, DEAD

2) NaOH, EtOH

70%, 99% e.e.

1) LiAlH4, THF, 85%

2) p-TsCl, Et3N, 80%

3) CH3CH2MgBr,

Li2CuCl4 70%

(R) - A or (S) - A

OH

(S) - 30; 20% overall yield; 99% e.e.

(R) - 30; 14% overall yield; 99% e.e.

Scheme 30.

O

O OH

(R) or (S)

p-TsCl, Et3N

DMAP, 88%

O

O OTs

PrMgBr

CuBr.Me2 S, 55.6%

O

O

MeOH

2N HCl, 99%

OH

HOp-TsCl, KOH

37%

OOH

(R)-30; 15% overall yield; 93% e.e.

(S)- 30; 92% e.e.

s-C3H7MgBr

CuI, THF, 82%


2.22. (9Z, 11E)-9,11-Hexadecadienal (31)

(9Z, 11E)-9,11-Hexadecadienal (31) is a componentof the sex pheromone of the sugar cane borer, Diatraeasaccharalis, an economically important pest distributedfrom Argentina to Cuba.108-110 Santangelo et al.111

reported the syntheses of all four possible isomers of31 employing one starting material, 9-decen-1-ol, via

divergent synthetic routes (17-26% overall yield)(Scheme 32).

2.23. 2-Methyl-1,6-dioxaspiro[4.5]decane (32)

The spiroketal 2-methyl-1,6-dioxaspiro[4.5]decane(32) was identified by Francke et al.112,113 as a minorpheromone component of the common wasp, Paravespula

Scheme 31.

HOOH

OH

OH

OH

OHO

O

O H

1) SnCl2, , 55%

2) NaIO4, NaHCO3, CH2Cl2, 61%

1) CH3CH2CH2PPh3B r,

n-BuLi, THF, 88%;

2) H2, Pd/CaCO3, hexane, 81%;

1) acidic Dowex® W50,H2O, 79%

2) p-TsCl, Py, 60%;

O

O

OH

TsO

s-C3H7MgBr,

CuI, THF, 78%.

OH

(R)-30

OMeMeO

8.8% overall yield; 99.5% e.e

Scheme 32.

1) Amberlyst-15, Et2O, DHP, 93%

2) Br2, CH2Cl2, 81%

3) NaNH2, THF, 98%

4) n-BuLi, THF, paraformaldehyde, 61%

HO7

7

1) LiAlH4, THF, 97%

2) MnO2, CH2Cl2, 63%

A

THPO

O

H7

1) PentylPPh3Br,

KHMDS, THF, 62%(20 :1 E, Z : E, E)

2) , EtOH, 97%Purification, > 99% (E, Z)

3) PDC, CH2Cl2, 70%

1) PentylPPh3Br, n-BuLi,

THF/Et2O, HCl, Et2O, 63%

(10 :1 E, E : E, Z)2) , EtOH, 97%

Purification, > 99% (E, E)3) PDC, CH2Cl2, 71%

O

H7

O

H7

(9E, 11Z) - 31

MnO2, CH2Cl2, 63%THPO

H

O

7

1) PentylPPh3Br,

KHMDS, THF, 62%(16 : 1 Z : E)

2) (Cyclohexyl)2BH,

H+/EtOH, 65%3) , EtOH, 97%

recristallization, > 99% (Z, Z)4) PDC, CH2Cl2, 71%

1) PentylPPh3Br, n-BuLi,

THF/Et2O, HCl, Et2O, 61%

(7 : 1 E : Z)2) (Cyclohexyl)2BH;

H+/EtOH, 68%3) , EtOH, 97%

Purification, > 99% (Z, E)4) PDC, CH2Cl2, 71%

O

H7

O

H7

A

(9E, 11E) - 31

(9Z,11E) - 31 (9Z,11Z) - 31

THPO

OH

26% overall yield from A; > 99% (E , E)26% overall yield from A; > 99% (E , Z)

18% overall yield from A; > 99% (Z, E) 17% overall yield from A; > 99% (Z, Z)

p-TsOH p-TsOH

p-TsOHp-TsOH


vulgaris. Zarbin et al.114 described a diastereoselectiveapproach to (2R,5S)- and (2S,5R)-32. The route employedan alkylation reaction between the cyclopentanone N,N-dimethylhydrazone and the chiral iodides (R)- or (S)-A,controlling the stereocenter at C-2 of the molecules. Thealkylated products were transformed into the 1,8-O-TBS-1,8-dihydroxy-5-nonanones in four steps, and a subsequentstereoselective spiroketalization in acidic media, affordeda diastereoisomeric mixture (1:2) of both isomers of 32(Scheme 33).

2.24. 2-Methyl-6-methylene-7-octen-4-ol (33) (Ipsenol)

Ipsenol 33 was identified as an aggregation pheromonecomponent of the bark beetle, Ips paraconfusus.115 Ceschiet al.116 described a short synthesis of (±)-ipsenol 33employing a selective indium insertion on a mixture of 2-bromomethyl-1,3-butadiene and its vinylic isomers, in36% overall yield (Scheme 33).

2.25. 5,9-Dimethylpentadecane (34)

The coffee leaf miner, Leucoptera coffeella, is aneconomically important pest of coffee trees in Brazil. Ithas been demonstrated by Francke and co-workers117 thatthe main component of the female-produced sexpheromone of this species is 5,9-dimethylpentadecane(34), however, the stereochemistry of the naturalpheromone remains unknown.

Moreira and Corrêa118 described an enantioselectivesynthesis of three stereoisomers of 34, from commercialisopulegol and synthetic neo-isopulegol67,92 (Scheme 35).

Zarbin et al.119 described a direct synthesis of racemic 34employing an unsymmetrical double Wittig olefination tobuild the carbon skeleton of the molecule as the key reaction.The bis-phosphonium salt, derived from 1,3-dibromopropane,was reacted sequentially in one pot with the ketones 2-octanone and 2-hexanone, affording the unsymmetrical diene.This was readily hydrogenated over Pd/C, furnishing a

Scheme 33.

HO OH

OH

n

1) LiAlH4, Et2O, 5 h, 85%

2) p-TsCl, Py, 58%3) KI, NaHCO3, 86%

4) TBSCl, Et3N, DMAP, 70%

I

TBSO H

(R) - A

OEt

O O1) Baker's yeast, 4d, 51% (94% e.e.)

2) DCC, DMAP, 3,5-DNBA, 50%3) Recrystalli zation (> 99% e.e.)

4) KOH (1 mol L-1 ), THF/EtOH 1:1, 90%5) LiAlH4, Et2O, 5 hs, 82%

OH

H OH 1) p-TsCl, Py, 58%

2) KI, NaHCO3, 86%

3) TBSCl, Et3N,

DMAP, 70%

(S) - A

N

N(CH3)2

1) n-BuLi, 0 °C, 30 min

2) (R) - A or (S) - A, THF, 90%3) CuCl2, THF, 73%

O OTBS

*1) m-CPBA, CH2Cl2, 98%

2) LiAlH4, Et2O, 70%

3) TBSCl, Imid., THF 68%4) PCC, Al2O3, CH2Cl2, 72%

TBSO

O

OTBS

* , CH2Cl2, 77%

O

O

O

O

or

(2R, 5S) - 32 (2S, 5R) - 32

d.r. = 2 : 1

> 99% e.e.

> 99% e.e.

17% overall yield from (R)-A or (S)-A

p-TsOH

Scheme 34.

OH

isoprene

Br2Br

Br DMPU Br + vinylic isomers

1) In, NaI, DMF,3-methylbutyraldehyde, 91%

2) NH4Cl/H2O


30 - 40%quant. yield


mixture of all possible stereoisomers of pheromone 34 in54% overall yield. (Scheme 36). Synthetic racemic 34 showedhigh biological activity when tested in field experiments.

2.26. cis- and trans-2-Methyl-5-hexanolide (35) and (4R,5Z)-5-tetradecen-4-olide (36)

cis-2-Methyl-5-hexanolide (35) is a component of thepheromone blend of the carpenter bee, Xylocopahirutissima,120 while (4R,5Z)-5-tetradecen-4-olide (36) is thesex pheromone of the Japanese beetle, Popillia japonica.121

Zarbin et al.122 proposed a general approach to the synthesisof chiral pheromone lactones from readily available starting

materials derived from 2-oxazolines. As an application, thediastereoselective synthesis of cis- and trans-35 and a formalsynthesis of (4R,5Z)-36 were described (Scheme 37).

2.27. (E)-2,4-Dimethyl-2-hexenoic acid (37)

(E)-2,4-Dimethyl-2-hexenoic acid (37) is a caste-specific substance present in the mandibular glands ofmale ants in the genus Camponotus.124 Fernandes et al.125

described a synthesis of 37 in 39% overall yield and highstereoselectivity by zinc-promoted reduction of 2-(bromomethyl) alkenoates derived from Baylis–Hillmanadducts (Scheme 38).

Scheme 35.

1) p-TsCl, Py, 72%

OBn

1) H2, Pd/C, MeOH, 73%

2) MsCl, Py, CH2Cl2, 91%

3) n-PrMgBr, Li2CuCl4,

THF, -78oC, 90%

(5S,9S) - 34

From(+)-neo-isopulegol

OTs

OBn

similarly

n-BuMgBr,

Li2CuCl4

n-EtMgBr,

Li2CuCl4

OBn

OBn

(5R,9S) - 34

(5S,9R) - 34

OH

(-)- isopulegol

OH

OBn

see scheme 15

16% overall yield

7,2% overall yield

6,5% overall yield

2) n-BuMgBr, Li2CuCl4

THF, -78oC, 90%

Scheme 36.

Br Br2.1 equiv PPh3, DMF, 92%

BrPh3P PPh3Br

(i) 1.1 equiv n-BuLi, - 90 °C

(ii) 1 equiv 2-octanone, - 90 °C to r.t.

(iii) 1.1 equiv n-BuLi, -90 °C

(iv) 1 equiv 2-hexanone, -90 °C to r.t., 64%

Pd/C, hexane,

H2 (30 psi), 93%34 54% overall yield


2.28. (Z)-7,15-Hexadecadien-4-olide (38)

(Z)-7,15-Hexadecadien-4-olide (38) was described byLeal et al.126 as the female sex pheromone of the yellowishelongate chafer, Heptophylla picea. Clososki et al.127

described an enzymatic synthesis of (R)- and (S)-38. Aknown lipase-catalysed enantiolactonization in the keystep afforded a common precursor for both enantiomersof the pheromone, in 92% e.e. [overall yield: 27% for(S)- and 18% for (R)-isomer) (Scheme 39).

2.29. (3Z, 6Z, 8E)-Dodecatrien-1-ol (39)

The subterranean termite, Heterotermes tenuis, is a pestof great importance for the Brazilian economy as it causesserious damages in commercial plantations of Eucalyptusspp. and sugarcane.128 (3Z,6Z,8E)-Dodecatrien-1-ol (39) hasbeen identified as a pheromone of several species of

subterranean termites.129,130 Batista-Pereira et al.131 describedthe synthesis and electroantennographic (EAG) bioassays of39 with H. tenius antennae (Scheme 40).

2.30. 1,5-dimethyl-6,8-dioxabicyclo [3.2.1]octane (40)(frontalin)

Frontalin (40), first isolated by Kinzer,132 is acomponent of the aggregation pheromone of the southernpine beetle, Dendroctonus frontalis Zimmerman, andwestern pine beetle, Dendroctonus brevicomis Le Conte.Through unambiguous syntheses of both enantiomers andbiological testing, Mori133,134 has shown that the absoluteconfiguration of the biologically active compound is(1S,5R)-40. dos Santos et al.135 described the synthesis of(±)-frontalin (40) in 65% overall yield, employing anorganocuprate generated by tellurium/lithium exchangein the key step (Scheme 41).

Scheme 37.

N

Oi) n-BuLi, THF, -78°C

I

HO H

(S)-A (from ref. 114)

N

O

OHH3O+ O

O

HO

O

H+

cis - 35 trans - 35

O

O

HO

O

H

cis - 35 trans - 35

(cis/trans = 7:3)

I

HO H

(R)-A (from ref. 114)

similarly

(cis/trans = 7:3)

N

O

O

O

I

i) n-BuLi, THF, -78°CO

O

N

O OO

HOH

H+, MeOH

Ref. 123O

O

36

+

B (from ref. 106)

78% overall from iodide (S)-A

80% overall from iodide (R)-A

85%92%

85% 60%

51% overall yield from iodide B

ii)

Scheme 38.

H

O

+ OCH3

O

DABCO, 72%

OH

OCH3

O

HBr, H 2SO4, 75%

OCH3

O

Br

1) Zn/AcOH, 88%

2) NaOH, MeOH/H2O, 83%

OH

O

37 39% overall yield


Scheme 39.

HO OH

O

OO

1) CrCO3, DMF/MeOH,

pH 7.0, BnBr, r.t., 17 h, 84%

2) NaBH 4, Et2O/MeOH,

-20 °C, 2h, 95%

3) PPL, Et2O, 30 °C, 24h, 74%

OO

O

OBn

1) Pd/C 10%, H2, 1 atm, 3h, 95%

2) BH3.DMS, THF, r.t., 2h, 90%

3) PCC, CH2Cl2, r.t., 2h 90%

OO

O

H

(S)-A; 92% e.e.

(S)- B

DIBAL-H, THF,

-78 °C, 2h, 71%

OHO

O

OBn

(R)- C

(S)-B, THF, -100 °C, 1.5 h, 60%

PPh36

(R)-C, THF, -100 °C, 1.5 h, 55%

OO

OO

(S) - 38

(R) - 38

(S)- A

Z/E = 96:4; 27% overall yield; 92% e.e.

Z/E = 96:4; 18% overall yield; 92% e.e.

Scheme 40.

Br1) Zn, THF, 0 °C

butyraldehyde, 65%

2) p-TsCl, Py, DMAP, 95%

OR

R = HR = Ts

t-BuOK, diglyme

50 °C, 86%E/Z = 2:1

OH

DHP, Amberlyst,

CH2Cl2, 0 °C, 98%

OTHP

1) n-BuLi, THF, -70 °Cparaformaldehyde,

-70 °C - r.t. 74%2) p-TsCl, Py, DMAP, r.t., 65%

OTHP

TsO

A

B

A + B

1) NaI, CuI, K2CO3,

DMF, r.t., 70%

2) Amberl yst, MeOH,

60 °C, 89%

OR

H2, Lindlar, MeOH,

quinoline, 70%

OH

(3Z, 6Z, 8E) - 39

+ (3Z,6Z,8Z) - 39 23% overall yield after separation of mixture

Scheme 41.

TeBu

OO1) n-B uLi

2)ThCu(CN)Li

-70 to -30 °C

Cu(Th)(CN)Li2

OO OOOTs

83%

OsO4 OO OH

OH79% O

O

(±)-40 65% overall yield

p-TsOH


2.31. (Z)-7-Dodecenyl acetate (41), (Z)-9-tetradecenylacetate (42), (Z)-11-hexadecenyl acetate (43), (E)-11-hexadecenyl acetate (44), and (E)-11-hexadecen-1-ol (45)

Acetates 41-43 have been described as componentsof the sex pheromone of the fall armyworm, Spodopterafrugiperda, an important economic pest of maize andother grass crops in North, Central, and parts of South

America.136 Batista-Pereira et al.137 examined thepheromone blend of a Brazilian population of femalesS. frugiperda and reported the synthesis of pheromonecomponents through alkylation of alkynes withbromoalcohols (34-46 % overall yield) (Scheme 42).

(E)-11-Hexadecen-1-ol (44) and (E)-11-hexadecenylacetate (45) have been recently described by Zarbin etal.138 as components of the sex pheromone of Lonomiaobliqua, one of the most important urban insects in Brazildue to the urticanting spines in the larval stage. This mothhas become of great importance in medicine because ofthe danger it represents.139 Compounds 44 and 45 weresynthesized employing alkyne chemistry (23 – 30% overallyield) (Scheme 43).

3. Conclusions and Perspectives

In conclusion, in the last 20 years projects involvingChemical Ecology and more specifically synthesis ofinsect pheromones have considerably grown in Brazil

Scheme 42.

HOOH

n

HBr, C 6H6,

60 - 63%

HOBr

n

3

2 eq. n-BuLi

HOn

H2, Lindlar, quinoline

75 - 85%n

HOAc2O, Py

90 - 95%41 n = 5

42 n = 7

43 n = 9

nAcO

34 - 46% overall yield; > 99% (Z ) isomer

Figure 2. Number of syntheses of insect pheromones developed andpublished by Brazilian research groups in the last two decades

0

1

1985 1995 2005

2

3

4

5

6

Scheme 43.

HO OH( )

6

HBr, C 6H6

60%

HO Br( )

6

DHP, p-TsOH

p-TsOH

83%

THPO Br( )

6

n-BuLi, A, HMPA

74%

OTHP( )

7, MeOH

83%

OH( )

7

Diglyme, LiAlH4

74%

OH( )

7

( )7

OHH2, Lindlar

97%

Ac2O, Py

82%

OAc( )

7

( )7

OAc

(E) - 44

(E) - 45

Ac2O, Py

86%

(Z) - 44

(Z) - 45

23% overall yield

30% overall yield

19% overall yield

26% overall yield

A


(Figure 2). Several research groups are also working inisolation and identification of pheromones of Brazilianinsect pests, which will certainly contribute for thedevelopment of the area in the near future.

Control of insects using pheromones is amultidisciplinary approach and requires efforts on manyfacets. Nowadays, there is a greater demand to produceenvironmentally sound and chemical residue-freeagricultural products, and the initial doubt and obstaclesagainst using pheromones for pest management havebeen overcome in recent decades.140

In Brazil, the research and the development of thisarea is still concentrating in the Academia. The challengetoday for the accurate monitoring and/or control of insectsusing pheromone is the production in large scale of thepheromone components and the development of properdispenser system, which would decrease the price of theblends and stimulate their use in the field. This would bea prerequisite to be able to defeat the army of insects inthe next decade. Acknowledgments

The authors are grateful to CNPq, IFS/OPCW, FundaçãoAraucária, FAPESP, and Embrapa for financial support.

References

1. Shani, A.; Chemtech. 1998, 28, 30.

2. Karlson, P.; Lüscher, M.; Nature, 1959, 183, 55.

3. Zarbin, P. H. G.; Corrêa, A. G.; Rev. Bras. Ecol. 1998, 6, 39.

4. Butenandt, A.; Beckmann, R.; Stamm, D.; Hecker, E.; Z.

Naturforsch. 1959, 14b, 283.

5. Silverstein, R. M.; Brownlee, R. G.; Bellas, T. E.; Wood, D. L.;

Browne, L. E.; Science 1968, 159, 889.

6. Rodin, J. O.; Silverstein, R. M.; Burkhold, W. E.; Gorman, J.

E.; Science 1969, 165, 904.

7. Mori, K.; Tetrahedron 1989, 45, 3233.

8. Mori. K.; Tetrahedron Lett. 1973, 3869.


10. Mori, K. In The Total Synthesis of Natural Products, vol.4;

ApSimon, J., ed.; John Wiley & Sons: New York, 1981.

11. Mori, K. In The Total Synthesis of Natural Products, vol.9;

ApSimon, J., ed.; John Wiley & Sons: New York, 1992.

12. Ishmuratov, G. Y.; Yakovleva, M. P.; Kharisov, R. Y.; Tolstikov,

G. A.; Rus. Chem. Rev. 1997, 66, 987.

13. Mori, K.; Chem. Commun. 1997, 1153

14. Mori, K.; Eur. J. Org. Chem. 1998, 1479.

15. Mori, K.; Chirality 1998, 10, 578.

16. Mori, K.; Acc. Chem. Res. 2000, 33, 102.

17. Mori, K. In Topics in Current Chemistry, Pheromone and Other

Semiochemicals, vol.1; Schulz, S., ed.; Springer-

Verlag:Heidelberg, 2005.

Arlene G. Corrêa received herPh.D. from the FederalUniversity of São Carlos (1991)and completed her postdoctoraltrainings with Dr. Paul A.Wender (Stanford University,CA, 1997). She is AssociateProfessor in Department ofChemistry at the University

Federal of São Carlos. Her research interests areisolation, identification and synthesis of insectpheromones; synthesis of bioactive natural products andanalogues employing combinatorial chemistry techno-logies and green chemistry. She is a member of theBrazilian Society of Chemistry and American ChemicalSociety.

José Augusto F. P. Villar, gra-duated in Chemistry at FederalUniversity of Parana in 2003.He is currently a PhD studentin Organic Chemistry at UFPR,working under the supervisionof Prof. Alfredo R. M. Oliveira.He was in 2006 a teachingassistant of Prof. Paulo H. G.

Zarbin in the Chemical Ecology course of the graduateprogram in Chemistry at UFPR.

Paulo H. G. Zarbin is an Asso-ciate Professor of theDepartment of Chemistry at theFederal University of Parana(UFPR), where served as chairof the graduate program in che-mistry for the years 2002-2004.Obtained his PhD in 1998 atFederal University of São

Carlos, with part of his thesis developed at the NationalInstitute of Sericultural and Entomological Science, inTsukuba, Japan. He is presently head of the Laboratoryof Semiochemicals at UFPR and member of the BrazilianChemical Society, Entomological Society of Brazil, andInternational Society of Chemical Ecology, where acts ascouncilor. His main research interest is focused on theidentification, synthesis, biosynthesis and field evaluationof insect pheromones and other semiochemicals.


18. Pilli, R. A.; Zarbin, P. H. G.; J. Braz. Chem. Soc. 2000, 11, U2

19. Tumlinson, J. H.; Hardee, D. D.; Gueldner, A. C.; Thompson,

A. C.; Hedin, P. A.; Minyard, J. P.; Science 1969, 166, 1010.

20. Souza, J. P. D.; Gonçalves, A. M. R.; J. Org. Chem. 1978, 43,

2068.

21. Burkholder, W. E.; In Pheromone Research with Stored-Product

Coleoptera; Wood, D.; Silverstein, E.; Nakajima, M., eds.;

Academic Press: New York, 1970.

22. Chuman, T.; Kohno, M.; Kato. K.; Noguchi, M.; Tetrahedron

Lett. 1979, 25, 2361.

23. Chuman, T.; Kato. K.; Noguchi, M.; Agric. Biol. Chem. 1979,

43, 2005.

24. Ono, M.; Onishi, I.; Chuman, T.; Kohno, M.; Kato, K. Agric.

Biol. Chem. 1980, 44, 2259.

25. Mori, K; Nomi, H.; Chuman, T.; Kohno, M.; Kato. K.; Noguchi,

M.; Tetrahedron 1982, 38, 3705.

26. Mori, M; Chuman, T.; Kohno, M.; Kato. K.; Noguchi, M.; Nomi,

H.; Mori, K.; Tetrahedron Lett. 1982, 23, 667.

27. Pilli, R. A.; Murta, M. M.; Synth. Commun. 1988, 18, 981.

28. Pilli, R. A.; Murta, M. M.; Mem. Inst. Oswaldo Cruz 1991, 86, 117.

29. Ferreira, J. T. B.; Marques, J. A.; Marino, J. P.; Tetrahedron:

Asymmetry 1994, 5, 641.

30. Kobayashi, Y.; Kitano, Y.; Takeda. Y.; Sato, F.; Tetrahedron

1986, 42, 2937.

31. Pilli, R. A.; de Andrade, C. K. Z.; Synth. Commun. 1994, 24, 233.

32. Bartlett, P. A.; Richardson, D. P.; Myerson, J.; Tetrahedron 1984,

40, 2317.

33. Pilli, R. A.; Riatto, V. B.; J. Braz. Chem. Soc. 1998, 9, 571.

34. Guss, P. L.; Tumlinson, J. H.; Sonnet, P. E.; Proveaux, A. T.; J.

Chem. Ecol. 1982, 8, 545.

35. Guss, P. L.; Sonnet, P. E.; Carney, R. L.; Branson, T. F.;

Tumlinson, J. H.; J. Chem. Ecol. 1984, 10, 1123.

36. Guss, P. L.; Sonnet, P. E.; Carney, R. L.; Tumlinson, J. H.;

Wilkin, P. J.; J. Chem. Ecol. 1985, 11, 21.

37. Ferreira, J. T. B.; Simonelli, F.; Tetrahedron 1990, 46, 6311.

38. Schmuff, N. R.; Phillips, J. K.; Burkholder, W. E.; Fales, H.

M.; Chen, C. W.; Roller, P. P.; Ma, M.; Tetrahedron Lett. 1984,

25, 1533.

39. Phillips, J. K.; Walgenbach, C. A.; Klein, J. A.; Burkholder, W.

E.; Schmuff, N. R.; Fales, H. M.; J. Chem. Ecol. 1985, 11,

1263.

40. Mori, K.; Ebata, T.; Tetrahedron 1986, 42, 4421.

41. Walgenbach, C. A.; Phillips, J. K.; Burkholder, W. E.; King, G.

G. S.; Slessor, K. N.; Mori, K.; J. Chem. Ecol. 1987, 13, 2159.

42. Pilli, R. A.; Murta, M. M.; Russowsk, D.; Boeckelmann M. A.;

J. Braz. Chem. Soc. 1991, 2, 121.

43. Pilli, R. A.; Riatto, V. B.; J. Braz. Chem. Soc. 1999, 10, 363.

44. Rocca, J. R.; Tumlinson, J. H.; Glancey, B. M.; Lofgren, C. S.;

Tetrahedron Lett. 1983, 24, 1889.

45. Rocca, J. R.; Tumlinson, J. H.; Glancey, E. M.; Lofgren, C. S.;

Tetrahedron Lett. 1983, 24, 1893.

46. Mori, K.; Nakazono, Y.; Tetrahedron 1986, 42, 6459.

47. Pilli, R. A.; Murta, M. M.; J. Org. Chem. 1993, 58, 338.

48. Mahajan, J. R. Tresvenzol, L. M. F.; J. Braz. Chem. Soc. 1993,

4, 179.

49. Hunig, S.; Benzig, E.; Lucke, E.; Chem. Ber. 1957, 90, 2833.

50. Jacobson, M.; Ohinata, K.; Chambers, D. L.; Jones, W. A.;

Fujimoto, M. S.; J. Med. Chem. 1973, 16, 248.

51. Aldrich, J. R.; Oliver, J. E.; Lusby, J. P.; Kochanski, J.;

Lockwood, A.; J. Exp. Zool. 1987, 244, 171.

52. Remington, J. E.; Insects of the World, Ridge Press, Inc: New

York, 1975.

53. Baker, R.; Borges, M.; Cooke, N. G.; Herbert, R. H.; J. Chem.

Soc., Chem. Commun. 1987, 414.

54. Baptistella, L. H. B.; Aleixo, A. M.; Liebigs Ann. Chem. 1994,

785.

55. Carlson, D. A.; Mayer, M. S.; Silhacek, D. L.; James, J.D.,

Beroza, M., Bierl, B.A.; Science 1971, 174, 76.

56. Marques, F. A; Zara, A. J.; Ferreira, J. T. B.; Bulhões, L. O. S.;

Org. Prep. Proc. Int. 1994, 26, 680.

57. Francke, W.; Bartels, J.; Krohn, S.; Schulz, S.; Baader, E.;

Tengo, J.; Schneider, D.; Pure Appl. Chem. 1989, 61, 539;

Zarbin, P. H. G.; Moreira, M. A. B., Haftmann, J.; Francke, W.;

Oliveira, A. R. M.; J. Braz. Chem. Soc. 2007, 18, 1048.

58. Monteiro, H. J.; Zukerman-Schpector, J.; Tetrahedron 1996,

52, 3879.


60. Webster, F. X.; Silverstein, R. M.; J. Org. Chem. 1986, 51,

5226.

61. Monteiro, H. J.; Stefani, H. A.; Eur. J. Org. Chem. 2001, 14,

2659.

62. Aldrich, J. R.; Oliver, J. E.; Lusby, W. R.; Kochansky, J. P.;

Borges, M.; J. Chem Ecol. 1994, 20, 1103.

63. Borges, M.; Aldrich, J. R.; J. Chem. Ecol. 1994, 20, 1095.

64. Borges, M.; Zarbin, P. H. G.; Ferreira J. T. B.; da Costa M. L.

M.; J. Chem. Ecol. 1999, 25, 629.

65. Borges, M.; Schimdt, F.; Sujii, E. ; Medeiros, M.; Mori, K.;

Zarbin, P. H. G.; Ferreira, J. T. B.; Physiol. Entomol.; 1998, 23,

202.

66. Mori, K.; Murata, N.; Liebigs Ann. Chem. 1994, 1153.

67. Ferreira J. T. B.; Zarbin, P. H. G.; Bioorg. Med. Chem. 1996, 4,

381.

68. Millar, J. G. In Topics in Current Chemistry, Pheromone and

Other Semiochemicals, vol.2; Schulz, S., ed.; Springer-

Verlag:Heidelberg, 2005.

69. Zarbin, P. H. G.; Reckziegel, A.; Plass, E.; Borges, M.; Francke,

W.; J. Chem. Ecol. 2000, 26, 2737.

70. Zarbin, P. H. G.; Reckziegel, A.; Plass, E.; Oliveira, A. R. M.;

Simonelli, F.; Marques, F. A.; J. Braz. Chem. Soc. 2000, 11,

572.

71. Krohn, S.; Fletcher, M, T.; Kitching, W.; Drew, R. A. I.; Moore,

C. J.; Francke, W.; J. Chem. Ecol. 1991, 17, 485.


72. Ferreira, J. T. B.; Zarbin, P. H. G.; J. Braz. Chem. Soc. 1996, 7,

143.

73. Mahajan, J. R.; Resck, I. S.; J. Braz. Chem. Soc. 1997, 8,

383.

74. Unelius, C. R.; Eiras, A.; Witzgall, P.; Bengtsson, M.;

Kovaleski, A.; Vilela, E. F.; Borg-Karlson, A. K.; Tetrahedron

Lett. 1996, 37, 1505.

75. Simonelli, F.; Oliveira, A. R. M.; Marques, F. A.; Silva, D. C.;

J. Braz. Chem. Soc. 1998, 9, 371.

76. Suzuki, T.; Agric. Biol. Chem. 1981, 45, 1357.

77. Suzuki, T.; Agric. Biol. Chem. 1981, 45, 2641.

78. Mori, K.; Kuwahara, S.; Ueda, H.; Tetrahedron 1983, 39, 2439.

79. Levinson, H. Z.; Mori, K.; Naturwissenschaften 1983, 70, 190.

80. Suzuki, T.; Kozaki, J.; Sugawara, R.; Mori, K.; Appl. Entomol.

Zool. 1984, 19, 15.

81. Zarbin, P. H. G.; Cruz, W. D.; Ferreira, J. T. B.; J. Braz. Chem.

Soc. 1998, 9, 511.

82. Santangelo, E. M.; Corrêa, A. G.; Zarbin, P. H. G.; Tetrahedron

Lett. 2006, 47, 5135.


84. Santangelo, E. M.; Zarbin, P. H. G.; Cass, Q. B.; Ferreira, J. T.

B.; Corrêa, A. G.; Synth. Commun. 2001, 31, 3685.

85. Brown, W. V.; Moore, B. P.; Insect Biochem. 1979, 9, 451.

86. Pilli, R. A.; Bockelmann, M. A.; Del Corso, A.; J. Chem. Ecol.

1999, 25, 355.

87. Zarbin, P. H. G.; Borges, M.; Santos, A. A.; Oliveira, A. R. M.;

Simonelli, F.; Marques, F. A.; J. Braz. Chem. Soc. 2000, 11, 424.

88. Côrrea-Ferreira, B. S.; Moscardi, F.; Entomol. Exp. Appl. 1996,

79, 1.

89. Pavis, C.; Malosse, C.; Ducrot, P.H.; Descoins, C.; J. Chem.

Ecol. 1994, 20, 2213.

90. Olaifa, J. I.; Kikukawa, T.; Matsumura, F.; Coppel, H. C.;

Environ. Entomol. 1984, 13, 1274.

91. Anderbrant, O.; Lofqvist, J.; Hogberg, H. E.; Hedenstrom, E.;

Baldassari, N.; Baronio, P.; Kolmakova, G.; Lyons, B.; Naito,

T.; Odinokov, V.; Simandl, J.; Supatashvili, A.; Tai, A.;

Tourianov, R.; Entomol. Exp. Appl. 2000, 95, 229.

92. Moreira, J. A.; Corrêa, A. G.; J. Braz. Chem. Soc. 2000, 11,

614.

93. Phillips, J. K.; Miller, S. P. F.; Andersen, J. F.; Fales, H. M.;

Burkholder, W. E.; Tetrahedron Lett. 1987, 28, 6145.

94. Levinson, H. Z.; Levinson, A.; Ren, A.; Mori, K.; J. Appl.

Entomol. 1990, 110, 203.

95. Mateus, C. R.; Feltrin, M. P.; Costa, A. M.; Coelho, F.; Almeida,

W. P.; Tetrahedron 2001, 57, 6901.

96. Bento, J. M. S.; Albino, F. E.; Della Lucia, T. M. C.; Vilela, E.

F.; J. Chem. Ecol. 1992, 18, 245.

97. Francke, W.; Schröder, W.; Curr. Org. Chem. 1999, 3, 407.

98. Howse, P. E.; Jones, O. T.; Stevens, I. D. R.; Insect Pheromones

and their Use in Pest Management; Chapman & Hall: London,

1998.

99. Schlyter, F.; Birgersson, G. A.; In Pheromones of Non-

Lepidopteran Insects Associated with Agricultural Plants;

Hardie, J.; Minks, A. K., eds.; CAB International: Wallingford,

1999

100. Francke, W.; Schröder, F.; Philipp, P.; Meyer, H.; Sinnwell, V.;

Gries, G.; Bioorg. Med. Chem. 1996, 4, 363.

101. de Sousa, A. L.; Resck, I. S.; J. Braz. Chem. Soc. 2002, 13,

233.

102. Perez, A. L.; Campos, Y.; Chinchilla, C. M.; Oehlschlager,

A. C.; Gries, G.; Gries, R.; Giblin-Davis, R. M.; Castrillo,

G.; Peña, J. E.; Duncan, R. E.; Gonzalez, L. M.; Pierce, H.

D., Jr.; McDonald, R.; Andrade, R.; J. Chem. Ecol. 1997,

23, 869.

103. Bartelt, R. J.; In Pheromones of Non-Lepidopteran Insects

Associated with Agricultural Plants; Hardie, J.; Minks, A. K.,

eds.; CAB International: Wallingford, 1999.

104. Giblin-Davis, R. M.; Gries, R.; Crespi, B.; Robertson, L. N.;

Hara, A. H.; Gries, G.; O’Brien, C. W.; Pierce, H. D.; J. Chem.

Ecol. 2000, 26, 2763.

105. Baraldi, P. T.; Zarbin, P. H. G.; Vieira, P. C.; Correa, A. G.;

Tetrahedron: Asymmetry 2002, 13, 621.

106. Zarbin, P. H. G.; Arrigoni E. D.; Reckziegel, A.; Moreira J. A.;

Baraldi, P. T.; Vieira, P. C.; J. Chem. Ecol, 2003, 29, 377.

107. Zarbin, P. H. G.; Princival, J. L.; Santos, A. A.; Oliveira, A. R.

M.; J. Braz. Chem. Soc. 2004, 15, 331.

108. Hammond, A. M.; ESA Meeting, Atlanta, GA, 1980.

109. Carney, R. L.; Lui, A. S. T. Patent Application No: US 1981-

242081 19810309, 1981.

110. Carney, R. L.; Lui, A. S. T. Patent No: US 4357474 A 1982;

98:125738b, 1983.

111. Santangelo, E. M.; Coracini, M.; Witzgall, P.; Corrêa, A. G.;

Unelius, R.; J. Nat. Prod. 2002, 65, 909.

112. Francke, W.; Reith, W.; Hindorf, G.; Angew. Chem. Int., Ed.

Engl. 1978, 17, 862.

113. Francke, W.; Hindorf, G.; Reith, W.; Naturwissenschaften 1979,

66, 618.

114. Zarbin, P. H. G.; Oliveira, A. R. M.; Delay, C. E.; Tetrahedron

Lett. 2003, 44, 6849.

115. Light, D. M.; Birch, M. C.; Naturwissenschaften 1979, 66,

159.

116. Ceschi, M. A.; Petzhold, C.; Schenato, R. A.; J. Braz. Chem.

Soc. 2003, 14, 759.

117. Francke, W.; Toth, M.; Szöcs, G.; Krieg, W.; Ernst, H.;

Buschmann, E.; Z. Naturforsch. 1988, 43C, 787.

118. Moreira, J. A.; Corrêa, A. G.; Tetrahedron: Asymmetry 2003,

14, 3787.

119. Zarbin, P. H. G.; Princival, J. L.; Lima, E. R.; Santos, A. A.;

Ambrogi, B. G.; Oliveira, A. R. M.; Tetrahedron Lett. 2004,

45, 239.

120. Wheeler, J. W.; Evans, S. L.; Blum, M. S.; Velthius, H. H. V.;

Camargo, J. M. F.; Tetrahedron Lett. 1976, 4029.


121. Tumlinson, J. H.; Klein, M. G.; Doolitle, R. E.; Ladd, R. E.;

Proveaux, A. T.; Science, 1977, 197, 789.

122. Zarbin, P. H. G.; Oliveira, A. R. M.; Simonelli, F.; Villar, J. A.

F. P.; Delay, Jr., O.; Tetrahedron Lett. 2004, 45, 7399.

123. Kang, S. K.; Shin, D. S.; Lee, J. O.; Goh, H. G.; Bull. Korean

Chem. Soc. 1986, 7, 444.

124. Brand, J. M.; Duffield, R. M.; MacConnell, J. G.; Blum, M. S.;

Fales, H. M.; Science 1973, 179, 388.

125. Fernandes, L.; Bortoluzzi, A. J.; Sá, M. M.; Tetrahedron 2004,

60, 9983.

126. Leal, W. S.; Kuwahara, S.; Ono, M.; Kubota, S.; Bioorg. Med.

Chem. 1996, 4, 315.

127. Clososki, G. C.; Ricci, L. C.; Costa, C. E.; Comasseto, J. V.; J.

Braz. Chem. Soc. 2004, 15, 809.

128. Arrigoni, E. B.; Almeida, L. C.; Kasten, Jr., P.; Precetti, A. A.

C. M.; Bol. Tec. Copersucar 1989, 48, 38.

129. Laduguie, N.; Robert, A.; Bonnard, O.; Vieau, F.; Le Quéré, J.

L.; Sémon, E.; Bordereau, C.; J. Insect Physiol. 1994, 40, 781.

130. Yamaoka, R.; Tokoro, M.; Hayashiya, K.; J. Chromatogr. 1987,

399, 259.

131. Batista-Pereira, L. G.; dos Santos, M. G.; Corrêa, A. G.;

Fernandes, J. B.; Dietrich, C. R. R. C.; Pereira, D. A.; Bueno, O.

C.; Costa-Leonardo, A. M.; J. Braz. Chem. Soc. 2004, 15, 372.

132. Kinzer, G. W.; Fentiman, F. A.; Page, F. T.; Foltz, R. L.; Vite, J.

P.; Pitman, G. G.; Nature 1969, 221, 477.


134. Wood, D. L.; Browne, L. E.; Ewing, B.; Lindalh, K.; Bedard,

W. D.; Tilden, P. E.; Mori, K.; Pitman, G. B.; Hughes, P. R.;

Science 1976, 192, 896.

135. dos Santos A. A.; Ferrarini R. S.; Princival, J. L.; Comasseto, J.

V.; Tetrahedron Lett. 2006, 47, 8933.

136. Andrews, K. L.; Flo. Entomol. 1988, 71, 630

137. Batista-Pereira, L. G.; Stein, K.; de Paula, A. F.; Moreira, J. A.;

Cruz, I.; Figueiredo, M. L. C.; Perri Jr., J.; Corrêa, A. G.; J.

Chem. Ecol. 2006, 32, 1085.

138. Zarbin, P. H. G.; Lorini, L. M.; Ambrogi, B. G.; Vidal, D. M.;

Lima, E. R.; J. Chem Ecol. 2007, 33, 555.

139. Duarte, A. C.; Caovilla, A. J.; Lorini, I.; Lorini, D.; Mantovani,

G.; Sumida, J.; Manfre, P. C.; Silveira, R. C.; Moura, S. P.; J.

Bras. Nefrol. 1990, 12, 184.

140. Boo, K.S.; Park, K.C.; Appl. Entomol. Zool. 2005, 40, 13.

Received: April 4, 2007

Web Release Date: September 28, 2007

FAPESP helped in meeting the publication costs of this article.

Paulo H. G. Zarbin,* José A. F. P. Villar and Arlene G. Corrêa 2007 review.pdf · Nesta revisão...

Documents

Transcript of Paulo H. G. Zarbin,* José A. F. P. Villar and Arlene G. Corrêa 2007 review.pdf · Nesta revisão...