Synthesis of 16-dehydropregnenolone derivatives and their...

CHAPTERS

Synthesis of 16-dehydropregnenolone derivatives and their biological activity

Chapter-S Synthesis of 16-dehydropregnenolone derivatives and their biological activity

5.1 Introduction

Malaria kills 1-2 million people each year and 300-500 million new clinical cases

of malaria are reported annually. 1 Malaria is a particularly devastating disease in sub-

Saharan Africa, where about 90% of cases and deaths occur. Malaria is also a serious

public health problem in certain regions of South East Asia and South America. Human

malaria transmitted by female Anopheles mosquitoes is caused by four species of

Plasmodium, which are, P. falciparum, P. vivax, P. ovale and P. malariae. Most cases of

malaria and deaths are caused by P. falciparum. The development of resistance to

mainstay drugs like chloroquine, and controlled use of new artemisinin analogs have

created an urgent need to discover new antimalarial agents. The life cycle, immunological

defense mechanisms, and clinical development of malaria in humans is a complex

process? Clinical malaria is characterized by periodic fever, which follows the lysis of

infected erythrocytes, and caused mainly by the induction of cytokines interleukin-1 and

tumor necrosis factor. P. falciparum infection can have serious effects, for example,

anemia, cerebral complications (from coma to convulsions), hypoglycemia and

glomerulonephritis. The disease is most serious in the non-immune individuals, including

children, pregnant women and tourists.

Pregnanes, the C-21 steroid derivatives, are an important class of bioactive

compounds having diverse pharmacological activity and which has provided interesting

'leads' for the development of new drugs. These potent pregnane derivatives have been

found to posses cytotoxic,3 antifeedant,4 anti-inflammatory,5•6 anti-asthamatic/ lipid

lowering8 and anti-viral9 activities. They also find use as neurosteroids10 and as inhibitors

of testosterone 7 a reductase11 which helps in the treatment of androgen sensitive prostate

cancer in men. 12 Besides this, a number of pregnanes are not only similar to cardiac

glycosides with respect to molecular and cellular site of action, but they have enhanced

cardiac contractibility. 13 Pregnane glycosides because of their remarkable

pharmacological activities are one of the major components of traditional Chinese

medicine. 14 These biologically active compounds isolated chiefly from Asclepiadaceae15

family plants have been found to posses anti-cancer, 16 anti-asthamatic, 17 anti-tumor18 and

anti-fungal activities. 19 The synthetic derivatives of this class of compounds are larger,

more hydrophilic, have increased efficacy and reduced toxicity relative to the parent

compound 20 and have primarily been used for the treatment of ulcerative colitis,21

Crohn's disease21 and cardiac contractibility.22 Owing to the immense importance of these

171

Chapter-5 Synthesis of 16-dehydropregnenolone derivatives and their biological activity

medicinally important pregnane derivatives, considerable attention is being devoted to the

synthesis and biological evaluation of this important class of compounds. 22- 29 In the

search of newer derivatives, the synthesis of novel pregnane derivatives in excellent yields

and anti-malarial activity is given below.

5.2 Chemical transformation of 16-dehydropregnenolone: The syntheses

of amine analogues of pregnenolone were accomplished by subjecting the naturally

isolated 16-dehydropregnenolone using various aromatic and aliphatic amine by

employing Michael addition reaction at 45°C for 4 h to afford amine derivative of

pregnenolone (1-9) in very good yield.

NH2R NHR

0

_)lo 45°C R1,o

45'Cl (~) R R1

1A --\~ Ac

18 --\~ H

2A \~ Ac lh-N\ 0 28 \~

_)lo ~0 lh-

H

4 ~~ 10 H I

5 \_~N, Ac

6 x-o H 7 :\~NH2 H 8 ~ H

"""" I

9 \~N~ H

l___

172


5.3 Anti-malarial Activity

Derivative of pregnenolone were screened for their in-vitro antimalarial activity

against chloroquine (CQ) sensitive 3D7 strain of P. falciparum. Chloroquine was used as

reference drug. Among the screen compounds (1-9), compound 4 showed activity.

Activity was evaluated at 10, 2 and 1 J..tg/mL. Compounds with MIC value :S 10 J..tg/ml are

given in Table 1.

Table 1. Anti-malarial activity of derivative of pregnenolone

S.No. Compound No. MIC p.tg/ml ICso

1 1A 10 >500

2 1B 10 >500

3 2A 2 415.2

4 2B 2 409,:0

5 3 >10 >500

6 4 :S2 180.79

7 9 :S2 >500

MIC= Minimum concentration inhibiting development of ring stage parasites into the

schizonts

5.4 Experimental section:

5.4.1 Representative procedure for the preparation of N-propylamine derivative of 16-

dehydropregnenolone (3P-Hydroxy-16a-(propylamino)pregn-5-en-20-one) (1)

Compound 1 was obtained from 16-dehydropregnenolone acetate (100 mg, 0.28 mmol)

and N-propylamine. N-propylamine was also used as solvent. The reaction mixture was

stirred for 4 h at 45°C. The reaction mixture was cooled, filtered and then extracted with

EtOAc and H20, the extract was evaporated under reduced pressure. Then the crude

product was chromatographed on silica gel to afford the desired compound lA and lB.

Yield: lA 45% and lB 40%

173


31J-Acetoxy-16a-(propylamino )pregn-5-en-20-one(lA)

( NH

0

,)lo

IR(KBr): 2937,1715,1112 cm-1• 1H NMR: (300 MHz, CDCh) bH 5.29 (1H, m, H-6), 4.53 (lH, m, H-3), 4.12 (lH, m, H-

16), 3.12 (br, NH) 2.71 (3H, m, H-17, 1 '), 2.32 (2H, m, H-4), 2.23 ( 3H, s, H-

21), 2.22 (3H, m, CH3CO ), 2.04 (lH, m, H-12), 1.97 (1H, m, H-7), 1.84 (4H,

m, H-1, 2, 2'), 1.68 (lH, m, H-15), 1.62 (2H, m, H-11, 2), 1.57 (1H, m, H-7),

1.47 (1H, m, H-11), 1.46 (1H, m, H-8), 1.43 (1H, m, H-12), 1.23 (lH, m, H-

15), 1.17 (1H, m, H-14), 1.10 (1H, m, H-9), 1.08 (lH, m, H-1), 0.96 (3H, s, H-

18), 0.96 (3H, t, J = 7.0 Hz, H-3'), 0.57 (3H, s, H-19). 13C NMR: (75 MHz, CDCh) () 206.0 (C-20), 170.5 (OCOCH3), 139.6 (C-5), 121.9 (C-6),

73.7 (C-3), 67.5 (C-17), 57.1 (C-16), 53.9 (C-14), 49.2 (C-9), 49.0 (C-1'), 45.1

(C-13), 38.3 (C-4), 38.0 (C-12), 36.8 (C-1), 36.5 (C-10), 31.4 (C-8), 31.4 (C-

7), 31.3 (C-2), 29.8 (C-21), 27.6 (C-15), 21.6 (OCOCH3), 20.7 (C-2'), 19.8

(C-11), 19.3 (C-18), 14.1 (C-19), 11.4 (C-3').

ESI-MS: (C26H4,N03), m/z 416 [M+Ht.

31J-Hydroxy-16a-(propylamino )pregn-5-en-20-one(2B)

( NH

IR(KBr): 3101,1715,1598, 1116cm-1• 1H NMR: (300 MHz, CD30D) bH 5.35 (1H, m, H-6), 4.17 (lH, m, H-16), 3.37 (1H, m,

H-3), 2.85 (3H, m, H-17, 1'), 2.27 (2H, m, H-4), 2.23 ( 3H, s, H-21), 2.04 (1H,

m, H-12), 1.97 (lH, m, H-7), 1.84 (4H, m, C-1, 2, 2'), 1.68 (lH, m, H-15),

174


1.62 (1H, m, H-11), 1.57 (1H, m, H-7), 1.48 (lH, m, H-2), 1.46 (1H, m, H-8),

1.47 (1H, m, H-11), 1.43 (1H, m, H-12), 1.23 (1H, m, H-15), 1.17 (lH, m, H-

14), 1.08 (1H, m, H-1), 1.03 (3H, s, H-18), 1.03 (3H, t, J = 6.9 Hz, H-3'), 0.98

(1H, s, H-9), 0.66 (3H, s, H-19). 13C NMR: (75 MHz, CD30D) b 207.4 (C-20), 142.6 (C-5), 121.86 (C-6), 72.4 (C-3),

68.9 (C-17), 58.4 (C-16), 55.6 (C-14), 51.6 (C-9), 49.9 (C-1 '), 46.3 (C-13),

43.0 (C-4), 39.5 (C-12), 38.5 (C-1), 37.8 (C-10), 32.8 (C-8), 32.6 (C-7), 32.3

(C-2), 31.5 (C-21), 30.6 (C-15), 22.0 (C-2'), 21.0 (C-11), 19.9 (C-18), 14.4

(C-19), 11.4 (C-3').

ESI-MS: (C24H39N02), mlz 374 [M+Ht.

5.4.2 Phenyl-1-propylamine derivative of 16-dehydropregnenolone (2A & 2B): using

similar procedure as described for lA, compound 2A and 2B were obtained from 16-

dehydropregnenolone acetate ( 100 mg, 0.28 mmol) and 3-phenylpropan-1-amine.

Yield: 2A 30% and 2B 40%.

3jl-Acetoxy-16a-(3-phenylpropylamino )pregn-5-en-20-one (2A)

1HNMR:

0

_)lo

(300 MHz, CDCh) bH 7.24 (2H, m, H-6', 8'), 7.14 (3H, m, H-5', 7', 9'),

5.30 (1H, m, H-6), 4.55 (lH, m, H-3), 4.01 (1H, m, H-16), 2.92 (1H, d=

6.1Hz, H-17), 2.79 (1H, m, H-1'), 2.68 (lH, m, H-1'), 2.58 (2H, t, J= 7.8

Hz, H-3'), 2.29 (2H, m, H-4), 2.16 (2H, m, H-7, 12) 2.08 (3H, s, H-21),

2.00 (3H, m, CH3CO ), 1.84 (4H, H-1, 2, 2'), 1.67 (1H, m, H-15), 1.63 (2H,

m, H-11, 2), 1.57 (1H, m, H-7), 1.46 (lH, m, H-8), 1.46 (1H, m, H-11),

1.36 (lH, m, H-12), 1.23 (1H, m, H-15), 1.08 (2H, m, H-1, 14), 0.95 (3H, s,

H-18), 0.90 (1H, m, H-9), 0.53 (3H, s, H-19).

175


13C NMR: (75 MHz, CDCb) o 205.9 (C-20), 170.5 (OCOCH3), 139.9 (C-5), 139.6 (C-4'), 128.7 (C-6', 8'), 128.5 (C-5', 9'), 126.5 (C-7'), 122.1 (C-6), 73.9 (C-

3), 67.9 (C-17), 57.3 (C-16), 54.0 (C-14), 49.2 (C-9), 47.2 (C-1 '), 44.9 (C-

13), 38.2 (C-4), 38.0 (C-12), 36.8 (C-1), 36.5 (C-10, 3'), 31.3 (C-8), 31.3

(C-7), 31.3 (C-2), 29.7 (C-21), 28.0 (C-2'), 27.7 (C-15), 21.5 (OCOCH3),

20.8 (C-11), 19.3 (C-18), 14.1 (C-19).

ESI-MS: (C321itsN03), mlz 492 [M+Ht.

3Jl-Hydroxy-16a-(3-phenylpropylarnino) pregn-5-en-20-one (2B)

1HNMR:

ESI-MS:

~ N

' H

HO

(300 MHz, CD30D) bH 7.29 (2H, m, H-6', 8'), 7.20 (3H, m, H-5', 7', 9'),

5.32 (1H, m, H-6), 4.05 {lH, m, H-16), 3.47 (1H, m, H-3), 3.06 (1H, d, J=

8.2 Hz, H-17), 2.80 (1H, m, H-1'), 2.74 (1H, m, H-1'), 2.69 (2H, t,J= 7.8

Hz, H-3'), 2.28 (2H, m, H-4), 2.20 (3H, s, H-21), 2.16 (2H, m, H-7, 12),

2.05 (3H, m, H-1, 2'), 1.88 (lH, m, H-2) 1.81 (1H, m, H-15), 1.70 (2H, m,

H-11, 2), 1.67 (1H, m, H-7), 1.46 (1H, m, H-8), 1.44 {lH, m, H-11), 1.36

(lH, m, H-12), 1.26 {lH, m, H-15), 1.13 (2H, m, H-1, 14), 0.99 (3H, s, H-

18), 0.88 (IH, m, H-9), 0.60 (3H, s, H-19).

(C3oH43N02), m/z 450 [M+Ht.

5.4.3 Morpholine derivative of 16-dehydropregnenolone (3): By similar procedure as

described for 1, compound 3 was obtained from 16-dehydropregnenolone acetate (100

mg, 0.28 mmol) and morpholine.

176


3~-Acetoxy-16a-(morpholino )pregn-5-en-20-one (3)

0

_)lo

1\ N 0 \__/

1H NMR: (300 MHz, CDCb) £5H 5.35 (1H, m, H-6), 4.58 (1H, m, H-3), 3.71 (4H, t, J =

4.4 Hz, H-3', 5'), 3.61 (lH, m, H-16), 2.74 (1H, d, J = 8.6 Hz, H-17), 2.53

(2H, m, H-2', 6' ), 2.32 (4H, m, H-4, 2', 6'), 2.18 ( 3H, s, H-21), 2.02 (3H, m,

CH3CO ), 2.02 (1H, m, H-12), 1.97 (lH, m, H-7), 1.84 (4H, H-1, 2), 1.68 (1H,

m, H-15), 1.62 (2H, m, H-11, 2), 1.57 (1H, m, H-7), 1.50 (lH, m, H-8), 1.50

(1H, m, H-11), 1.50 (lH, m, H-12), 1.18 (1H, m, H-15), 1.13 (lH, m, H-14),

1.04 (1H, m, H-1), 1.00 (3H, s, H-18), 0.86 (1H, m, H-9), 0.64 (3H, s, H-19).

ESI-MS: (C27H41N04), m/z 444 [M+Ht.

Yield: 50%

Dodecan-1-amine derivative of 16-dehydropregnenolone (4): By similar procedure as


mg, 0.28 mmol) and dodecan-1-amine.

3~-Hydroxy-16a-( dodecylamino) pregn-5-en-20-one ( 4)

HO

H N

1H NMR: (300 MHz, CD30D) £5H 5.27 (lH, m, H-6), 4.02 (1H, m, H-16), 3.44 (lH, m,

H-3), 2.90 (1H, d, J= 7.1 Hz, H-17), 2.68 (2H, m, H-1'), 2.22 (2H, m, H-4),

2.22 (3H, s, H-21), 2.04 (1H, m, H-12), 1.96 (lH, m, H-7), 1.83 (4H, m, H-1,

2, 2'), 1.69 (1H, m, H-15), 1.64 (lH, m, H-11), 1.55 (1H, m, H-7), 1.47 (lH,

177


m, H-2), 1.47 (lH, m, H-11), 1.46 (1H, m, H-8), 1.44 (1H, m, H-12), 1.25-1.18

(20H, H-14, 15, 3'-11') 1.08 (lH, m, H-1), 0.95 (3H, s, H-18), 0.84 (3H, t, J=

6.9 Hz, H-12'), 0.98 (lH, s, H-9), 0.58 (3H, s, H-19). 13C NMR: (75 MHz, CD30D) 8 206.4 (C-20), 140.8 (C-5), 121.1 (C-6), 71.5 (C-3), 68.2

(C-17), 57.1 (C-16), 54.1 (C-14), 49.5 (C-9), 47.6 (C-1'), 45.1 (C-13), 42.1

(C-4), 38.5 (C-12), 37.2 (C-1), 36.7 (C-10), 32.0 (C-8), 32.0 (C-7), 31.6 (C-2),

31.5 (C-21), 30.0 (C-15), 29.8-29.3 (C-3'-10') 26.5 (C-2'), 22.8 (C-11'), 21.0

(C-11), 19.5 (C-18), 14.2 (C-19), 14.2 (C-12').

Yield: 50%.

ESI-MS: (C33Hs7NOz) m/z 500 [M+1t

5.4.5 Di-Methylamino ethylamine derivative of 16-dehydropregnenolone (5): By

similar procedure as described for 1, compound 5 was obtained from 16-

dehydropregnenolone acetate (100 mg, 0.28 mmol) and N,N-dimethylethane-1,2-diamine.

3fl-Acetoxy-16a-(2-( dimethylamino )ethylamino) pregn-5-en-20-one(5)

3' \

1' N-3,

G· NH 0

)lo

1H NMR: (300 MHz, CDCh) JH 5.30 (1H, m, H-6), 3.92 (1H, m, H-16), 3.46 (lH, m, H-

3), 2.90 (2H, t, J= 6.0 Hz, H-1'), 2.75 (lH, m, H-17), 2.50 (2H, t, J= 6.0 Hz,

H-2') 2.42 (6H, s, H-3'), 2.17 (2H, m, H-4), 2.16 (3H, s, H-21), 2.03 (3H, m,

CH3CO ), 1.94 (1H, m, H-7), 1.90 (1H, m, H-12), 1.85 (1H, m, H-2), 1.82 (lH,

m, H-1), 1.68 (1H, m, H-15), 1.62 (2H, m, H-11, 2), 1.60 (2H, m, H-15), 1.57

(1H, m, H-7), 1.57 (lH, m, H-12), 1.47 (lH, m, H-11),1.46 (lH, m, H-8), 1.14

(lH, m, H-14), 1.02 (IH, m, H-1), 1.00 (lH, m, H-9), 0.96 (3H, s, H-18), 0.58

(3H, s, H-19).

178


13C NMR: (75 MHz, CDCh) i> 209.5 (C-20), 179.9 (OCOCH3), 142.4 (C-5), 122.1 (C-6),

72.4 (C-3), 72.0 (C-17), 58.3 (C-16), 57.0 (C-2'), 55.9 (C-14), 51.0 (C-9), 38.0

(C-1 '), 45.9 (C-13), 45.4 (C-4'), 43.0 (C-4), 39.4 (C-12), 37.7 (C-1), 37.6 (C-

1 0), 31.4 (C-8), 32.3 (C-7), 31.3 (C-2), 31.5 (C-21 ), 24.5 (C-15), 21.6

(OCOCH3), 19.8 (C-11), 19.3 (C-18), 14.4 (C-19).

ESI-MS: (C27H44N203), mlz 445 [M+Ht.

Yield: 50%.

5.4.6 Benzylamine derivative of 16-dehydropregneno/one (6): By similar procedure as


mg, 0.28 mmol) and phenylmethanamine.

3fl-Hydroxy-16a-(benzylamino) pregn-5-en-20-one (6)

p NH

HO

1H NMR: (300 MHz, CD30D) c:5H 7.34-7.21 (SH, m), 5.35 (lH, m, H-6), 3.85 (1H, m, H-

16), 3.71 (1H, d, J = 12.2 Hz, H-1 '), 3.59 (1H, d, J = 12.2 Hz, H-1 '), 3.51 (1H,

m, H-3), 2.5 (1H, d= 6.5 Hz, H-17), 2.27 (2H, m, H-4), 2.16 (3H, s, H-21),

2.16 (1H, m, H-12), 1.97 (1H, m, H-7), 1.84 (2H, m, H-1, 2), 1.68 (1H, m, H-

15), 1.62 (1H, m, H-11), 1.57 (1H, m, H-7), 1.48 (lH, m, H-2), 1.46 (1H, m,

H-8), 1.46 (lH, m, H-11), 1.43 (1H, m, H-12), 1.24 (1H, m, H-15), 1.16 (1H,

m, H-14), 1.08 (lH, m, H-1), 1.01 (3H, s, H-18), 0.98 (1H, s, H-9), 0.66 (3H,

s, H-19). 13C NMR: (75 MHz, CD30D) i> 208.8 (C-20), 141.0 (C-5), 139.5 (C-2'), 128.7 (C-3', 7'),

128.5 (C-4', 6'), 127.4 (C-5'), 121.4 (C-6), 72.2 (C-3), 71.7 (C-17), 57.7 (C-

16), 54.8 (C-14), 53.0 (C-1'), 50.1 (C-9), 45.1 (C-13), 42.4 (C-4), 39.0 (C-12),

37.4 (C-1), 36.7 (C-10), 32.8 (C-8), 32.0 (C-7), 31.7 (C-2), 31.7 (C-21), 31.7

(C-15), 21.0 (C-11), 19.6 (C-18), 14.6 (C-19).

179


MS (EISMS): (C2sH39N02) m/z 422 [M+ It.

Yield: 60%.

5.4. 7 Propane-1,3-diamine derivative of 16-dehydropregnenolone (7): By similar

procedure as described for 1, compound 7 was obtained from 16-dehydropregnenolone

acetate (100 mg,0.28 mmol) and propane-1,3-diamine.

3Jl-Hydroxy-16a-(3-aminopropylamino) pregn-5-en-20-one (7)

HO

1H NMR: (300 MHz, CD30D) t5H 5.33 (1H, m, H-6), 4.00 (lH, m, H-16), 3.57 (1H, m,

H-1 '), 3.37 (1H, m, H-3), 2.85 (2H, t, J = 5.9 Hz, H-3'), 2.55 (1H, d, J = 8.8

Hz, H-17), 2.27 (2H, m, H-4), 2.23 ( 3H, s; H-21), 2.05 (lH, m, H-12), 1.96

(lH, m, H-7), 1.85 (4H, m, C-1, 2, 2'), 1.67 (1H, m, H-15), 1.62 (1H, m, H-

11), 1.57 (1H, m, H-7), 1.48 (lH, m, C-2), 1.47 (1H, m, H-11), 1.45 (1H, m,

C-8), 1.43 (1H, m, H-12), 1.22 (1H, m, H-15), 1.17 (lH, m, H-14), 1.08 (1H,

m, C-1), 1.03 (3H, s, H-18), 1.03 (3H, t, J= 6.9 Hz, H-3'), 0.98 (lH, s, H-9),

0.66 (3H, s, H-19).

ESI-MS: (C24~oN202), m/z 389 [M+t.

Yield: 40%.

5.4.8 Heptan-2-amine derivative of 16-dehydropregnenolone (8): By similar procedure

as described for 1, compound 8 was obtained from 16-dehydropregnenolone acetate (1 00

mg, 0.28 mmol) and heptan-2-amine.

180


31J-Hydroxy-16a-(heptan-2-ylamino) pregn-5-en-20-one (8)

~ NH

HO

1H NMR: (300 MHz, CD30D) bH 5.37 (1H, m, H-6), 4.17 (1H, m, H-16), 3.37 (1H, m,

H-3), 2.85 (2H, m, H-17, 2'), 2.27 (2H, m, H-4), 2.24 ( 3H, s, H-21), 2.04 (1H,

m, H-12), 1.96 (lH, m, H-7), 1.84 (4H, m, H-1, 2, 3'), 1.68 (1H, m, H-15),

1.62 (1H, m, H-11), 1.57 (1H, m, H-7), 1.48 (lH, m, H-2), 1.47 (1H, m, H-11),

1.46 (1H, m, H-8), 1.43 (1H, m, H-12), 1.31 (2H, m, H-6'), 1.23 (lH, m, H-

15), 1.22 (4H, m, H-4', 5') 1.17 (1H, m, H-14), 1.08 (1H, m, H-1), 1.02 (3H, s,

H-18), 1.00 (3H, t, J= 6.8, H-7'), 0.99 (1H, s, H-9), 0.67 (3H, s, H-19).

MS (ESIMS): (C2sH47N02), m/z 430 [M+Ht.

Yield: 40%.

5.4.9 Di-ethylamino propylamine derivative of 16-dehydropregnenolone (9): By

similar procedure as described for 1, compound 9 was obtained from 16-

dehydropregnenolone acetate (100 mg, 0.28 mmol) and N,N-diethylpropane-1,3-diamine.

31J-Hydroxy-16a-(3-( diethylamino )propylamino) pregn-5-en-20-one (9)

(

/N~

5'

1'

NH

HO

181


1H NMR: (300 MHz, CDCh)


41\U

j l l I i I

NH 0

)l_o ~

ESI-MS of compound lA

H-·1-A PROTON CPC13 iD:\cdri} u.s~r 35

NH

0 ~

_.JV\.. _ __._)l__o _,._,._)Lu_wj~ ~ ~~~•Tj'~'~*'~*'~•~~~~·~~~·~H~n~•rj~~>~H~>~•~~~~·~H~•~•~•~r~~~"lP'~"~'~"~"~!~"*~o~•~n~•J~'~.~n~>~H~fJ~'~"~~

10 9 8 7 6 S 4 3 2 Oppm

(~I (~\ (~) ~~~~ 1~1 r~h~( (j)(~)

I f i

1H NMR spectrum (300 MHz, CDCh) of compound lA

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13C NMR spectrum (75 MHz, CD30D) of compound lB

ESI-MS of compound 2A

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5.5 References:

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