Baran Group Meeting Guaianes and Xanthanes …Baran Group Meeting Guaianes and Xanthanes Emily...

OO

Emily CherneyBaran Group Meeting Guaianes and Xanthanes

O

OO

O

farnesyl pyrophosphate

guaianeskeleton

xanthaneskeleton

xanthanolidesguaianolides

Examples: Mundane to Exotic

pseudoguaianes aromadendrane cubebane/ivaxillarane

patchoulane alerenane

1OPP

3

14

4

5 6 7 8

10

1112

13

15

92

13

14

4 5

67

810

11121315

92 13

14

45

67

810

111213

15

92

86

1212

Prevalence and Biosynthesis:

The Bioactivity...- Both groups possess activity that could treat: cancer, ulcers, inflammation, fungal infections, malaria, and leishmaniasis - Possess endoperoxides with similar antimalarial activity to artemesinin- Thapsigargin, a xantholide, currently undergoing phase I clinical trials for breast, kidney, and prostate cancer. Englerin A is a highly selective inhibitor of renal cancer cell growth.

Around the world with Guaianes and Xanthanes:

Bedfordiasalicina

Plucheadioscoridis

Inulaverbascifolia Naphthea

charboliiXanthium

strumarium

Gergeriaafricana

Xanthiumspinosum

Xanthiumcatharticum

Related but Not Discussed:

Me

MeMe

Me

guaiazulene

Me

Me CH2OO

OH

H

tamaparthin-α-peroxide

Me

O

OMe

Me

O

AcO

H

geigerin acetate

O

O

O

hypocretenolide

6

12

812

12

5

H2C

H2C OO

HO

O

H

HOR

clementein

Me

Me

H

H

O O

hanalpinol

OH

O

O

ClHOAcO

O

OO

xanthipungolide

15-chloro-2-epi-xanthanol

The Nature of the Beast:• Sesquiterpenes represent the largest class of terpenes, and guaianolides comprise of the the largest and most widely distributed groups of sesquiterpenoid lactones (JACS (1984) 8217)• Over 500 guaianes isolated by 1990 (100's more since then), dozens of dimeric guaianes (even trimers observed) • 112 xanthanes/xanthanolides, only 11 non-lactonized xanthanes and 3 known dimeric xanthanes• Synthetic challenges include: medium ring synthesis, dense stereochemical complexity on a relatively flexible skeleton, difficult levels of oxidation, NPs possess epimerizable centers and reactive moieties

Wise words from Clayton Heathcock (circa 1973):

Source: The Total Synthesis of Natural Products, Volume 2, pages 199 and 395

"the sesquiterpene field is an excellent area for the testing and refining of new synthetic methods and concepts"

"one may confidently design stereoselective syntheses in the decalin area, in which the relative stereochemistry is established by either kinetic or thermodynamic methods.

Stereoselective design in the hydroazulene area is much more difficult"

fun fact: the 1st sesquiterpene total synthesis was Ruzicka's farnesol in 1923

via:

germacrene

generallycis

generallytrans

Emily CherneyBaran Group MeetingGuaianes and Xanthanes

Photochemistry and Santonin: Synthesis of Podoandin: Blay et al. JOC (2000) 6703.

Many earlier syntheses begin with a photochemical rearrangement of Santonin based on work by Barton and co-workers (J. Chem. Soc. (1957) 929)For the true seminal work on photochemistry of santonin see: Villavecchia, Atti R. Accad. Lincei (1885) 722, Cannizzaro, et. al. ibid, (1886) 450

O

O

O

AcOH, aq.h!

O

O

O

via:

HO

O

O

OAcH

santonin "isophoto-santonic lactone"

(30-38%)

O

O

O

OAcH

OAc

Synthesis of 3-Oxa-guaianolides: Blay et al. Tetrahedron (2000) 633.

1) TsNHNH22) catecholborane

O

O

OAcH 1) O3

2) NaBH4

(68%)

O

O

O

OAcH

HO

1) MsCl2) NaPhSe3) H2O2

O

O

O

OAcH

H2C

(89%)

(73%)

O3, Ph3P

O

O

O

OAcH

O

TsOHor Al2O3

O

O

O

OH

1) LiAlH4 2) MsCl, pyr.

O

O

OAcH

H H

HHH(97%)(91 %)

(88%)

O

O

O

OAcH

O

O

O

OAc

1) Red-Al2) TPAP, NMO

(75%)

O2, h!,methylene blue

(37%)

O

O

O

MeO

O

O

OH4 steps

6

12

6

12

AcOH, aq.h!

(85%)O

O

OH OAc

1) NaTeH2) NaBH4

(60%)

O

O

HOH OAc

H

1) POCl32) LiBr-Li2CO3

(72%)O

O

H OAc

HO

O

H

TsOH, SiO2PhMe, H2O

(85%)

podoardin

santonin

Synthesis of Absinthin: Zhang et al. JACS (2005) 18. Isolated in 1953, structure elucidated in 1985, first and only total synthesis

O

O

O

OAcH

"isophoto-santonic lactone"

1) NaBH4, MeOH2) ArSeCN, PBu33) NaIO4

(47%)

O

O

OAcH

10 days, neat, rt

(72%)

O

O

OAcH

O

O

OAc

H

H

H

O

O

HO H

O

O

HO

H

H

H

1) KOH2) SOCl2, EtN33) OsO4, NMO4) NaIO45) MeLi

(55%)

See Also: Gutekunst 2009 GM "Traditional Chinese Medicine"

Barton's proposalNote: mechansim proven to be radical

"isophoto-santonic lactone"

For Other Furanoguaianolide Studies See: Tetrahed. (2003) 1877, TL (1988) 4521, J. Chem. Soc. Perk. Trans. 1 (1990) 1601

DBU

MsO

O

1

5

12

8

absinthin


Synthesis of (+)-Ainsliadimer: Lei et al. OL (2010) 4284.

Diversity oriented synthesis: Ando et al. J. Nat. Prod. (1994) 433.

O

O

O

OAcH

isophoto-santonic lactone

1) Pd/C, H22) NaBH43) MsCl, Pyr.

(52%)

O

O

OAcH

H

1) KOH2) SOCl2, DABCO

(93%)

O

O

H

H

1) LDA, (PhSe)22) H2O2, AcOH (85%)

O

O

H

H

m-CPBACHCl3, 0-10°C

(63%)

O

O

H

HO

1) Al(OiPr)3,

PhMe, µW

2) DMP

(32%)

O

O

H

H

O

dehydro-zaluzanin C

estafiatin

(!)-BINOL,neat, 50 °C,

60 h

Hetero-DA70%

O

O

H

H

O

OO

HH

O

HCl aq.,THF

(73%)

O

O

H

H

O

OO

HH

OOH

DBU

(89%)

O

O

H

H

OO

HH

OOH

HO

(+)-ainsliadimer

Santonin without Photochemistry:

O

O

Osantonin

12steps

(19%)

O

O

OMs0.5 M KOAcAcOH, reflux

O

O

H

H

(24%)

O

O

H

isocostuslactone

dihydrokauniolide

(32%)

mCPBA

O

O

H

H

(58%)1) LDA, PhSeCl2) H2O2

(32%)O

O

O

H

HO

estafiatin

1) LDA, (PhSe)22) H2O2

(80%)

O

O

H

H

isodehydro-costuslactone

CrO2(tBuO)2

(27%)

O

O

H

H

O

2-osodesoxyl-igustrin

1 eq.mCPBA

O

O

H

O

O

H

O

O

(36%)

(22%)

1,10-epi-arborescin

1) LDA, PhSeCl2) H2O2

(51%)

O

O

HO

3,4-epiludartin

Al(OiPr)3,

PhMe, "

(50%)

O

O

H

HO

8-deoxy-11,13-dihydrorupicolin B

1) LDA, (PhSe)22) H2O2

(27%)

O

O

H

HO

8-deoxyrupicolin B

1 starting material,15 natural products

ainsliatrimer A:OL (2008) 5517

OO

H

O

O

O

H

O

O

O

HO

HOH

+

+


Assymetric Synthesis of Pleocarpenene: Snapper et al. JACS (2007) 486.Photochemistry without Santonin:Synthesis of Dehydrokessane: Liu et al. TL (1977) 3699.

O

AcO

MeO2C

AcO

PhH, h!;TsOH

(450 w Hg Lamp,pyrex filter)

O H

H

CO2Me

OAc(60%)

MeMgBr, CuI,

Et2O, 0 °C

(56%)

O H

H

CO2Me

OAc

1) BF3•OEt2,

HSSH

2) Raney Ni

H

H

CO2Me

OAc

(62%)

LiAlH4

(95%)

H

H OH

OH

TsCl, Pyr., rt

O

H

H

(83%)

NaH,

MeO

O

OMe

O

H

H

O

OMe

NaH, MeLi

O

H

H

HO

(57%)

Hg(OAc)2, NaBH4

(61%)

O

H

H

O

LiAlH4 (quant.)

HO

H

H

OPOCl3, Pyr.O

dehydrokessane

O

O

MeO2CPhH, h!;Fe2(CO)9

(64%)

Fe(CO)3

CO2Me

1) DIBAL-H2) MnO23)

Fe(CO)3

HO

(76%)

CO2MeGrubbs II2.5 mol%

(94%)

HO

CO2Me

make assym.with MnO2; CBS reduction

CAN,acetone

(80%)HO

H CO2Me

H

HO

CO2Me

H

H

" #(1: 2.7 ":#)

1) LiAlH42) TIPSCl, DMAP Et3N; Ac2O (87%)

H

AcO

H OTIPS Cu(acac)2 (5 mol%)EDA; NaOEt

(93%) H

HO

H OTIPS

EtO2C

(COCl)2, DMSO;Et3N; MeMgCl

(79%)

H

H OTIPS

HO

HO

PhH, 200 °CDBU (15 mol%)

H

OH

HO

OTIPS

1) Raney Ni, H22) TBAF3) TsCl, Et3N, DMAP4) NaI, DBU

(51%)

(76%)

H

OH

HO

pleocarpene

O3; DMS; NaOMe

(51%)

H

H

OH

O

HOH

pleocarpenone

Fe(CO)3

MgBr


Synthesis of (+)-Chinensiolide B: Hall et al. JACS (2010) 1488.Syntheses from Carvone:Synthesis of Thapsivillosin F (highlights): Ley et al. ACIEE (2003) 5996.

O

H

(S)-carvone

1) H2O2, NaOH2) LiCl, TFA3) DHP, PPTS

(73%)

O

HTHPO

Cl

NaOMe

(95%)

THPO

H

HCO2Me

5 steps

TBDPSO

H

H

OMOM

OH

TBDPSO

H

H

OMOM

TESO OEt

3 stepsGrubbs II (2.5 mol%)

TBDPSO

H

H

OMOM

TESOOEt

17 stepsO

H

H

OAc

HO O

O

OH

O

OO

thapsivillosin F

Studies toward Thapsigargin : Massanet et al. OL (2006) 2879.

(see also Ley's work on thapsigargins: PNAS (2004) 12073)

O

(+)-dihydrocarvone

O

KOH, O2

(70%)O

OH

O

OH

DDQ

(70%)

1) Burgess

2) AD-mix !tBuOH:H2O

(74%)

O

OH

OH

h",AcOH

(93%)

H

H

OAc

O

OH

OH

H

H

OAc

O

1) OsO4, NMO, MeSO2NH22) TEMPO, NaClO, NaClO2

O

HO

OH

O

(60%) 6 7

12

6 7

12

O

H

(R)-carvone

1) H2O2, NaOH2) LiCl, TFA3) TBSOTf, Pyr.

O

HTBSO

Cl

NaOMe

(85%)(95%)TBSO

CO2MeH

H

1) LiAlH42) (COCl)2, DMSO, Et2N

(76%)

TBSO

CHOH

H

OTBDPS CO2Me

Bpin

BF3•OEt2 (2.5 mol%)TBSO

HO

O

TBDPSO

(87%*)*yield based on Z only,

E unreactive

(3.5:1 Z:E)

(>19:1 dr)

1) TBAF, AcOH2) p-NO2-PhSeCN,PBu33) H2O2

(42%)

TBSO

HO

O

1) Grubbs II (5 mol%)2) mCPBA

(84%)TBSO

O

H

H

O

1) DIBAL-H; LiEt3BH2) MnO2

TBSO

O

H

H

O

O

OH

(50%)

O

O

H

H

O

OH

PDC, TMSCl

(71%)

(+)-chinensiolide B

allylboration/lactonization

(~4:1 dr)

deprotection/oxidation


Organoiron approach: Donaldson et al. TL (2009) 1023.Making the fused 5-7 ring system Part 1:When 5 Leads

Synthesis of (±)-7-epi-!-bulnesene: Ovaska et al. TL (2002) 1939.

OMe2CuLi,

TMSCl, Et3N

OTMSCsF,

Br

(57%) (60%)

O

(rel. stereochem.)

CeCl2

OH

(57%)

MeLi (5 mol%)PhOEt, 155 °C

HO

(84%)

PPh3

DMSO

H

(50%)

(±)-7-epi-!-bulnesene

Approach to Geigerin: Jacobi et al. JOC (1992) 6305.

O

CO2MeMeO2C

1) PhSeCl2) H2O23) ethylene glycol,TsOH

(32%)

CO2MeMeO2C

O

O

1) NaOH, aq.2) (COCl)2, K2CO3, DMF3) Me-alaninate, Pyr.

(60%)MeO2C

O

O

O

HN

MeO2C

1) P2O52) BF3•OEt2

HSSH

(58%)

MeO2C

S

S

NO

OMe

1) DIBAL-H

2) nBuLi,

O3) (COCl)2, DMSO4) Li

5) TBSOTf, Et3N

N

O

S

S

OTBSOMe

OMe

1) PhH, "2) TBAF3) Hydroquinone, NaHCO3, "

OOMe

OMe

O

S

S

OTBDPS

Br

Mg, THF;

Fe+

(CO)3MeMeO2C

TBDPSO

Fe(CO)3

PF6

HMeO2C

H2O2,HO-

TBDPSO

MeO2C

H

1) LiAlH42) C6Me3H3, 200 °C

(43%)

(57%)

TBDPSO

OH

H

O

O

O

H

7 steps

Synthesis of Sundiversifolide: Shindo et al. OL (2008) 1247. (continued)

Making the fused 5-7 ring system Part 2:When 7 Leads (continued)

OH

1) TBDPSCl, imid. DMAP

2) nBuLi, (CH2O)n

3) Red-Al

4) MsCl, Et3N; NaI

OTBDPS

(82%)

N O

OO

Bn LDAN O

O O

BnOTBDPS

I

(92%)

AD mix-!

MeSO2NH2tBuOH/H2O

(97%)

O

OOTBDPS

OH

O

OI

OTBS

1) TBSCl, imid. DMAP2) TBAF. AcOH3) MsCl, Et3N; NaI, Acetone

O

OTBDPSTBSO

(82%)

1) tBuLi

2) TBDPSCl,

imid. DMAP

(88%)


Syntheses of (±)-Geigerin: Depres et al. ACIEE (2007) 6870.

Synthesis of Sundiversifolide: Shindo et al. OL (2008) 1247. (continued)

O

OTBDPSTBSO

1)

2) 6M HCl

MgBrOH

OTBDPSHO

( 87%)

1) TPAP, NMO2) TBAF

(>99%)O

OHHO

PPh3

O

O

CF3xylene

(92%)

HOO

O

4 stepsO

OH

HO

(+)-sundiversifolide

Synthesis of Dehydrocostus Lactone: Rigby et al. JACS (1984) 8217.

O 2 eq. O

OBrMg

then NaBH4

OH

OO(85%) (96%)

NaH, MeI

OMe

OO

50% aq TFA(77%)

OMeH

H(rel. stereochem.)

O

1) Li, CH3NH22) MEMCl

(82%)

OMeH

HMEMO

mCPBA

(54%)

OMeH

HMEMO O

1) LiCH2COLi22) TMSCl, NaI(62%)

OHH

HHOO

O

1) Swern [O]2)

P

S

N(Me)2

Ph CH2Li

then MeI, Pyr.(41%)

H

HO

O

Eschenmoser'ssalt;

"quaternization/elimination"

(71%)

H

HO

Odehydrocostus

lactone

BF4

MeLi, 0! 20 °C

(83%)

Me

Cl3C

O

ClZn, ultrasound

Me

O

Cl

Cl

H

H

CH2N2;DMSO

MeH

Cl

O

(52%)2 steps

OTBSMeO

LiClO4 (cat.)

MeH

Cl

O

HO(dr at C7: 85:15)

7

H Me

CO2Me

1)

2) DMDO, -90 °CTsOH

(49%)3 steps

MeH

Cl

O

O

OMeB(OH)2, Pd(OAc)2, dpdb, K3PO4

(58%)

MeH

Me

O

O

O

LiOH, H2O/THF, CO2;I2, KI, NaHCO3

MeH

Me

O

HO

I

O

O

nBu3SnH, BEt3(53%)2 steps

MeH

Me

O

HO

O

O

Ac2O, pry.,DMAP

MeH

Me

O

AcO

O

O

(±)"geigerin

(rel. stereochem.)

(±)"geigerin acetate

Making the fused 5-7 ring system Part 2:When 7 Leads (continued)

12

6 12

8


Synthesis of (+)-Achalensolide (highlights): Mukai et al. JOC (2008) 1061.

Studies Highlights 1: Lee et al. TL (2001) 1695.

Making the fused 5-7 ring system Part 3:Simultaneous Formations:

THPOLi

1)THPO

CHO

2) LiAlH4•

OTHP

HO

1) NaH, BnBr, TBAI (cat.)2) TsOH3) Swern [O]

•

O

BnO

O LiTBSO1)

2) VO(acac)2, tBuOOH;Ac2O, DIPEA, DMAP

O•

O

OBn

AcO

OTBS

(68%) (73%)

(52%)

DBU, DCM, rt

HO O

O

OTBS

Studies Highlights 2: Wender et al. OL (1999) 137.

Studies Highlights 3: Lee et al. OL (2010) 548.

HO

•2.5 mol% [Rh(CO)2Cl]2,

DCE, 80 °C

(76%)

HO

H

H

1) DMP2) MeMgBr

H

HHO

(+)-dictamnol

EtO

OO

O

ZnI2,Et2NH

(20%)

(See Wender's resiniferatoxin in Classics II)

(78%)

OE

H

OE=CO2Et

4 steps

H

(±)-clavukerin A

O

OO 1)nBuLi, BF3•OEt2,

2) PivCl, Pyr.TMS

O

O

OPiv

TMS

9steps

(65%)

•

OPivMOMO

10 mol% [RhCl(cod)]250 mol % dppp, 1 atm CO, PhMe, !

(96%)

OMOM

OPiv

O

10 stepsO O

O

H

(+)-achalensolide

Clever Metathesis Strategies:Sesquiterpene Aklaloid Synthesis: Craig et al. Eur. JOC (2006) 3558.

6steps

(R)-citronellene

O N

OO

iPr

1) NaHMDS;

BrTBDPSO

2) HCl, MeOH

O N

OO

iPrHO(79%)

Grubbs II5 mol%

(>99%)

O N

OO

iPr

HO1) NaOMe2) DMAP, DIC

CO2H

Ts

CO2Me

O

O

Ts

KOAc, BSA, PhMe, µW, 160 C°

CO2Me

Ts

(71%) (77%)

1) O3, PPh32) NH3 in EtOH3) MeMgBr

NHO

(+)-cananodine

(46%)

[5+2]

Michael/Conia-ene

Pauson"Khand-Type


Synthesis of Teucladiol: Vanderwal et al. JACS (2009) 15090.

Synthesis of (!)- Dihydroxanthatin: Morken et al. OL (2005) 3371.

Clever Metathesis Strategies:

HO Br

Me 8 steps TBSO

Me OH

10% Pd(OAc)2,2.5 eq Cu(OAc)2

BuO

O

Me

TBSO

OBu

O

Pd(II)BuO

MeR

Oshima-Utimoto

1) 9-BBN, H2O22) Dess-Martin

(68%)

O

Me

TBSO

OBuO

1) Ph3PCH2Br, tBuOK

2) TBAF

O

Me

HO

OBu

1) Dess-Martin

2) tBuOK

(92%)(85%)

N2 PO(OMe)2

O

Me

O

3) H2CrO4

Grubbs II (5 mol%)

O

O

Me

could not alkylate successfully

1) LDA, MeI2) Grubbs II (5 mol%) methyl vinyl ketoneO

O

MeO

(76%) 70%)

(59%)(!)-dihydroxanthatin

Synthesis of (+)-8-epi-Xanthatin: Martin et al. OL (2005) 4621.

12steps

MeO

O

OH

TIPS O

OMe

OTBSTBAF

(78%)O

Me

O

Grubbs II (5 mol%)methyl vinyl ketone (10 eq)DCM (0.005 M)

O

O

MeO

(+)-8-epi-Xanthatin

(83%)

Br

TMS

i. tBuLi; ii. CuCN;

iii. cyclopentenone

MO

TMS

iv. O

HOH

H

H

O

(60%)>10:1 dr trans-

selective

anti-aldol

Felkin-Anh

1) TESCl2) Grubbs II (5 mol%)

(77%)

O

TMS

H

TESO

O H

TESO

1) MeLi, CeCl32) TsOH

(60%)87:13 dr

HO HHO

(±)-teucladiol

Synthesis of Clavukerin: Metz et al. Eur. JOC (2010) 6145.

OHC

(S)-citronellal

O

NH

PhPh

OMe

HO

HO

CO2Et

(20%) (20%)

OHC

O

(90%)

CBr4, PPh3, DCM(94%)

O

Br

Br

Grubbs II (4 mol%)

H2C CH2

H

(!)-clavukerin A

(78%)(55%)

PPh3+CH3Br-

nBuLi

TBS

TBS


Synthesis of (±)-7-epi-!-Bulnesene: Negishi et al. JOC (1997) 1922.

Synthesis of (+)- Cladantholide: Lee et al. JACS (1997) 8391.

Free Radical Strategies:

Synthesis of (±)-Kessane: Booker-Milburn et al. OL (2003) 3309.

CO2Me

THPO

(4 steps from carvone)

1) DIBAL-H2)

MgBr THPO

HO

Br

OEt

Br Et3N,DMAP

THPO

O Br

OEt

nBu3SnH,

AIBNTHPO

O

H

OEt

H5-exo;7-endo

1) TsOH2) PCC

O

O

H

OEt

H

1) LDA, TMSCl2) DMDO

(77%) (98%)

(99%)(80%)

(79%)

O

O

H

OEt

H

HO 1) TsNHNH22) MeLi3) Jones [O]4) LDA, MeI

(18%)O

H

O

H

O

(+)- Cladantholide

Synthesis of (±)-Alismol: Lange et al. JOC (1999) 6738.

O

MeO2C

OO

h"

(53%)

H

H

CO2Me

H OO

O

1) iPrMgBr

2) LiAlH4

3) I2, PPh3

(50%)

H

H HO

O

I

OH

MeLi; CS2;MeI

(90%)

H

H HO

O

I

OCS2Me

nBu3SnH,

AIBNH

HO

O(92%)

1) Acetone, H+

2) MeMgBr, CeCl3

(50%)

H

HOH

(±)-alismol

(nBu)2ZrCp2ZrCp2

H

1) nBuNC

2) I23) HCl

(68%)

H

H

I

O

1)

2) PCC

TMS MgBr

H

I

O

TMS

nBu3SnH,

AIBN

H OTMS

(78%)

1) KH, H2O

2) iPr=PPh3

H

(46%3 steps)

(±)-7-epi-!-bulnesene

O

HO1) TMSCl, DMPU,

MgBrthen Et3N2) Et2Zn, CH2I2

(76%)

OTMS

HO

Fe(NO3)3

H

H O

1) Ph3P

2) BH3•THF; PCC3) Cp2TiCl2,AlMe3

(54%)

H

H

OH

OH

(#:! 1:2.5)

with the #$epimer:

NISH

H

O

I

Pd/C, H2

H

H

O(67%

2 steps)

(±)-kessane

For an interesting synthesis of bulnesene from patchoulol see: TL (1975) 4495


Christmann Synthesis Highlights: ACIEE (2009) 9105.

The Battle of Englerin A :Quick stats: Isolated in 2009 [OL (2009)p.57] and promptly patented; selectively inhibits renal cancer cell lines selectively with GI50 values of 1-87 nM; 4 total synthesis to date 1 in 2009 and 3 in 2010, 1 formal synthesis in 2010.

O

Me H O

H CHO2 steps from

cis-nepetalactone

1)BrZn

2) LiAlH4

Me H

H

OH

OH

OH4

steps

(85%)

Me H

H

Me

OO

Grubbs II(20 mol%)

Me H

H

Me

OO

3 steps

Me H

H

Me

HOO

O

O

OTBS

!

MeH

HMe

O

O

HO

O

OTBS

(99%)

2 steps

(+)-

en

gle

rin

A

Me H

HMe

O

O

O

O

OH

O

Ph

(")-englerin A

Ma Synthesis Highlights: ACIEE (2010) 3513.

OHC

5steps

OH

O

AuCl, DCM, rt

(48%)

15 steps10.9% overall

Me

HMe

O

OH

(")-englerin A

10steps


Echavarren Synthesis Highlights: ACIEE (2010) 3517.

OH

(R)-citronellal

geraniol

8steps

OH

O

OTES

[iPrAuNCPh]SbF6

Me

HMe

O

OH

OTES9

steps

(")-e

ng

lerin

A

18 steps7% overall

Nicolaou/Chen Synthesis Highlights: JACS (2010) 8220.

O

OBn O

Me

MsCl, DIPEA;

CO2Et

Me

O

CO2Et

OBnO

(7 steps)

14steps

(")-englerin A


Theodorakis Formal Synthesis Highlights: OL (3708) 3708.

O

O

O

O

O

N2

TBSO

Rh2(Ooct)4(2 mol%)

(90%)

Me

O

TBSO

O

O

O

O14

steps Ma'sintermed.

7steps

(")-englerin A

22 stepsoverall yield

???

if completed as depicted:

Baran Group Meeting Guaianes and Xanthanes …Baran Group Meeting Guaianes and Xanthanes Emily...

Documents

Transcript of Baran Group Meeting Guaianes and Xanthanes …Baran Group Meeting Guaianes and Xanthanes Emily...