Stereoselective synthesis of (−)-canadensolide from D-glucose

Tefrahdrot~ Vol.47.No. 3,pp.519-524.1991 rhcd increstBritain

STERE~~~ELE~T~VE~YNTHE~I~

0F 6k-~ANADEN~~LIDEFROM

G V M Sharma*and Sreenivasa Indian Institute of Chemical Technol~y,

Rao Vepachedu Hyderabad 500 007, India

(Received in UK 26 September

A simple and stereoseiectfve synthesrs through a radical medtated cychsatton,

Abstract:

(-)Canadensohde canadense

and

ment

carrred

et

was

al

2

Its

1 has

a total

A of

the

of

synthetrc

required

the

retrosynthetlc

tlve

formatron

could

I

from

design

on sugar,

unusual

easrly

the

interestmg

this

bond,

3 as shown

of

whrle such

m Sceme

stereoselectrve

mvolves

the

exomethylene

srmultaneously

to

mcorporatmg

as extension

Yoshrokr

et

al 3 have from

system

.

Herein

present

C-C

constructron

As

can be envisaged

the

regro-

from

and stereoselec-

exomethylene

at C-5

a

we report

and stereoselective

the

of side-cham

asslgn-

whrle

stereoselectrve

group. lead’

Pemcillmm

syntheses

b&butyrolactone) 2-7 syntheses a regro-

D-glucose,

structural

studtes,

total

would

from

gross

Fraser-Retd

employing

(2)

Isolated

. It’s

syntheses. rts

several

mtermedrate

by transformations

by

from

degradatrve

a-methylene in

system

mtroductlon

radrcal

4R

D-glucose

for

the

and

umque

avarlable

and

startmg

was

fungi’

a racemrc

resulted

cychsatlon.

the

C-C

2S,3R

and

whrch

metabolite against

spectral by

medtated

and

analysis of

usmg

as

attention

skeleton

be obtamed

at C-2

The

by a radtcal

mould

stereochemistry

1990)

of f-)-canadenosofide has been described.

activity

McCorkindale’

stereochemistry

much

syntheses

bond formatron

occurring

antrgerminatlve

relatrve

precursor.

attracted

a naturally

show by

its

absolute

carbohydrate m

to

out

estabhshed

assrgned

(l),

found

D-GLUCOSE

group.

and radrcal

2

generatron

1.

Scheme

I Extensiq

H

r

. .

o

Ojidlse

:0

nC4Hg =+

nc4Hg~ocb

-

‘&

H”XH dH

O\/

\

Deoxygenation

0

2

1 For as

the

m

the

of

olefm

extension reaction

the

present

appropriate chain site

extension as well

on aldehyde wrth

purpose,

startmg

umt

whrle as 4,

aldehyde because

49, the

hydrogenation

liberation obtamed

of in

with C-5

of

a benzyl

aldehyde

olefmic

free

hydroxy

4 steps

from

n-propyltriphenylphosphonlum

3

bromrde

519

bond

at

C-3.

D-glucose and

ether

at

C-3

functronahty

In 5 simultaneously Thus,

,

was

n-&L1

the

frrst

achieved in

posttron

would

THF

was

serve

as

lead

t,

obfectlve

of

by a Wlttrg to

afford

5

chosen

a handle saturation side-cham

olefmatron as

an

E/Z

520

G. V. M. SHARMAand

mixture m

In

51%

ethanol

yield

afforded

(Scheme

6,

2).

where

Catalytic

S. R. VEDACHEDU

hydrogenatron

debenzyiatron

also occured

Scheme

of resultant

olefm

srmultaneously

at

5 wrth C-3

10%

to grve

Pd-C

a free

II

H OH e

12 R =CH3”

CH3

12

R=H

“I

hydroxy

compound,

as its

propargyl

7. This propargyl different

At

for

C-3,

would

thus stage

wtth

C-3

NaH

which

to our advantage

the

lead

generation

group

m 6 was protected

bromrde

at later

group during the transformations

at

would

hydroxyl

and propargyl

of I through the intramolecular

rt was armed

of sugar,

transformations.

be taken

viz. as a protecting

carbon skeleton

hydroxy

further

, on reactron

dertvatrve

group at

functions

the required

C-2

requtred

ether

m THF

stages,

at C-I,

to afford

to perform

two

C-2 and to provtde

radrcal cyclrsation.

of

to the -crs-fused

radrcal

mtermedrate 10

brcyclo[3.3.0kctan

2 obtamable system

from

10, leading

to I. Accordingly Amberltte Mel

Hf

was converted

the crucral to afford

radical

at

reflux

tion

of

wrth

cont.

Alternatively

tn 50% m EH2C12

a stepwlse

Cr03-pyrrdine

8 tn 74%

brcychc

the brcychc

bIs(l,4-butyrolactone)

Cr03-pyridme

hydroxyl

afford

at

C-2

yreld,

was achieved

by methanolysrs

whrch on treatment

with

of 7 wrth

NaH,

CS2 and

xanthate ester 9 m 80% yield. As antrcrpated compound 9 underwent II,12 with n-Bu3SnH and cat. amount of AIBN m refluxmg benzene cychsation

obtamed

HCI

of free

to

to the

the desired -crs-fused

Havmg

wrth

the liberation

resin

system

aq. at

AcOH 40°C

compound 10 as a single stereorsomer

compound leading

10 m pure form,

It was next

to

to the

1. Accordmg

and srmultaneous afforded

a complex

OxldattOn of IO was undertaken.

m CH2Ci2

at

40°C

to

afford

oxldatron mixture

of

plan,

yield.

armed at the introducacrd hydrolysis

resultant

along with

Accordmgly

12 tn 74%

the

m 84% yield.

iactol

1 m very

10 was subjected Hydrolyses

of

the

of

10

ill)

wrth

poor

yreld.

to oxrdatron lactone

12

521

Synthesis of (-)-canadensolide

with

cont.

HCI in 50% aq. AcOH and oxidation

70% yield, whose spectral

of resultant

data were in full agreement

lactol

(13) with

with reported

PCC furnished

1 in

values3.

Experimental I ments

H NMR spectra

using deutero

on Perkm-Elmer

were

recorded

chloroform

683 or

FT 80-A,

Mass spectra

and VG Micromass

Jeol

PMX 90 or Bruker

with TMS as internal

1310 spectrophotometer.

DIP 360 or 370 polarimeter. spectrometer

on Varian

as solvent

Optical

were

standard.

rotations

recorded

were

on Fmnigan

and

cooled

measured

solution)

(0”) suspension

mmol)

and stirred

mixture

was was

quenched

washed

with

with

by column

chromatography

as an bZ

mixture.

1.90-2.44

for

dropwise

ammonium

brine,

(silica

was treated

dried 5%

hydrogenation filtrate

gel,

chloride

solution

(Na2S041

in pet.ether)

6 0.99 (t, 3H, CH3),

at

40 psi and

1.20-1.64

(m,

(d, lH, H-l).

room

12H), 2.00 (brs, IR(Neat):

temperature

3450 cm-’

A solution ture.

After

30 mm. propargyl

The reaction Orgamc cation

mixture

layer

7) in 78% yield

mixture

‘H NMR(CDC13): (C

as a liquid.

(EC).

Analysis

calcd.

(silica

‘H NMR(CDC13): 60.98

gel,

0.91, CHC13).

tempera-

at 0°C and stirred

solution

and extracted

Evaporation

5% EtOAc

of sodium

at room

in pet.

IR(Neat):

1 h.

with ether.

of solvent ether)

for

and purifi-

afforded

7 (1.1

(m, 12H1, 2.88 (t, lH1, 3430 (C&H)

and 2120

&I, -52.5 (c 1.2 g, CHC131.

for Cl1 H 22 0 4.* C, 60.52; H, 10.16. Found: C, 60.30; H, 10.3%.

A mixture at

to a suspension

(t, 3H, CH31, 1.24-1.76

Methyl-54eoxy-5-C_(n-propyl)-3-O43’-propynyl~,fkD-xylo

heated

chloride

and dried (Na2S04).

(m, 3H), 4.64 (d, IH), 5.90 (d, IH, H-l).

M+ 239 (M+-15).

and

(7):

(0.726 g, 6 mm011 was added

chromatography

was filtered

to

6 0.98 (t, 3H, CH3),

in dry THF (10 mL.) at 0” and stirred

brine

subjected

(m, 2H, H-3 and H-41, 4.48 (d, IH, H-2), 5.88

with aq. ammonium

with water,

by column

3.90 (d, lH), 4.10-4.24 cm-’

was quenched

was washed

of residue

bromide

1.56 (s, 3H, CH3),

(20 mL) was

7 h. The reaction

for

(OH). M+ 20 (M+-CH3). [&I, -12.5

50% suspension)

residue

hl, -99.4 (c 1.17, CHC13).

of 6 (1.2 g, 5.5 mmol) in dry THF (10 mL) was added

(0.480 g, 10 mmol,

Orgamc

of the

H-2), 5.01 (m, lH, H-41, 5.60-5.90

5-Deoxy-l,2-O-isopropylidene-5-C_(n-propyl~-20-(3 hydride

ether.

5 (2.2 g) in 51% yield

1.36 (s, 3H, CH3),

(5, 2 g) in ethanol

6 (1.22 g) in 86% yield. IH, OH), 3.95-4.24

2.8N

4 (3 g, 14.3

(6):

(0.2 g) and olefm

furnished

with

Purification

resulted

15

I h. The reaction

and extracted

and evaporated.

7.40 (brs, 5H, Ph). M+ 289 (M+-CH3).

of 10% Pd-C

(5.8 g,

of aldehyde

for an additional

3.92 (d, IH, H-31, 4.8 (s, 3H, PhCg2,

6.01 (d, IH, H-l),

on evaporation

focussing

with n-BuLi (5.3 mL, 15 mmol;

and stirred

EtOAc

bromide

30 min. A solution

5-Deoxy-l,2-O-isopropylidene-5-C_(n-propyl)-orDxylofuranose A suspension

on a JASCO

(5):

n-propyltriphenylphosphonmm

temperature

1H NMR(CDC13):

(m, 2H, allyhc),

(m, 2H, olefmic),

aq.

water,

of

N2 atmosphere

at room

in dry THF (10 mL) was added

layer

recorded

7070H instrument.

mmol) in dry THF (30 mL) under hexane

were

Mat 1210 double

3-0-Benzyl-5,6-dideoxy~-C~thyl-I,2-O-isopropylidenet-~xyl~x-5~~fura A stirred

WH 300 mstru-

IR spectra

reflux

fumanoside

of 7 (I g, 3.9 mmol)

and Amberhte

for

mixture

8 h. The reaction

was

H+ resm cooled,

(8):

(0.6 g) in methanol

flltered

and

washed

(15 mL) was with

methanol.

522

G. V. M. SHARMA and S. R. VEFWHEDU

Filtrate

was evaporated

two fractions Fraction

and residue

A: [o-anomer

1.20-1.73

purified

by column

chromatography

(slllca

gel) to give 8 m

in 79% yield. &,

0.4 g, 8% EtOAc In pet.

(m, 6H), 2.44 (t, IH), 2.82 (brs,

(d, IH). IR(Neat):

3420-3450

ether).

‘H NMR(CDCl3):

IH), 3.44 (s, 3H), 3.9 (m,

(OH), 3130 (C F-H)

and 2120 cm-’

6 0.98 (t, 3H, CH3),

IH), 4.06-4.31

(m, 3H), 4.92

(r.Z C). M+ 197 (M+-0CH3).

[a],

+68.4 (c 1.03, CHC13). Fraction

B: g-anomer

1.76 (m,

8b, 0.310 g, 9% EtOAc m pet.

12H), 2.47 (t,

ether).

‘H NMR(CDC13): 60.98 (t, 3H), 1.22(m, 3H), 4.79 (s, IH). [al,

IH), 3.44 (s, 3H), 4.0 (m, lH), 4.25-4.70

-70”

(c 1.15, CHC13). Methyl-5-deo~-2-~(S-~thylthio)~i~~~nyl~5-C~n~r~yl~~~~rop~yf~a,8-~xylofur~~ (9): A strrred

suspension

(5 mL) at 0” under mL) and strrred at

for

chloride

and extracted

Solvent

was evaporated

m pet ether)

Ethereal

layer

mixture

by column

0.91 (t,

pet. ether)

g, I.2

to O”, treated quenched

water,

with with

brme

chromatography

mmol)

m THF (5 was added

methyl aq.

rodrde

ammomum

and dried (Na2S04).

(srhca

gel, 4% EtOAc

3H), 1.20-1.70

(m, 6H), 2.25 (t,

IH), 2.57 (5, 3H), 3.22 (s,

3130 (C K-H)

and 2130 cm -I (EC).

[cd, +78.4 (c 0.575, CHC13). 60.9

of 9 (0.159

under N2 atmosphere

30

m dry THF

(t, 3H), 1.20-1.80

(m, 6H), 2.39 (t, IH), 2.48 (s, 3H), 3.4 (5, 3H), -120.5 (C 2.52, cHc13).

of 9

A solution of AIBN

(0.691

was

was washed with

was purlfled

50% drspersron)

of 8 (0.22 g, 1 mmol)

1 h It was cooled Reaction

(m, 2H), 4.46 (d, 2H), 4.97 (s, IH), 5.8 (s, 1H). [d,

Cyclization

mm.

benzene

to afford ‘H

Analysrs calcd.

was

at reflux

evaporated

and

(5 mL) contammg

and treated

residue

catalytic

amount

wrth n-Bu3SnH (0.174 g, 0.6 mmol).

chromatographed

(srhca

gel,

5% EtOAc

In

IO (0.089 g) In 84% yield. (m, 6H), 3.21-3.54

(m, 3H), 3.8-3.95

(m, 2H),

(m, 2H), X0-5.1 (m, 2H). M+ 212 [al,-8.31k 0.8% CHC13).

for Cl2 H 2. 0 3.. C, 67.89; H, 9.50. Found: C, 67.77; H, 9.27%.

‘H NMR(CDC13):

IH), 4.20-4.61

g, 0.5 mmol) m dry benzene was heated

NMR(CDCI~): 6 0.90 (t, 3H), 1.10-1.80

4.50 (m, IH), 4.6-4.85

8 -anomer:

1.2 mmol,

9 (0.254 g) m 80% yield.

‘H NMR(CDCI~):

4.10-4.25

and after

and residue

g,

wrth a solutron

(m, 4H), 5.21 (d, IH), 5.66 (t, IH). lR(Neat):

M+ 287 (M+-OCH3). B -anomer:

(0.0576

for 30 mm. Carbondlsulphlde

temperature.

wrth ether.

to afford

3H), 4.20-4.53

a-anomer

room

‘H NMR(CDCI~):~

a-Anomer:

After

temperature

1 h at

hydride

was treated

at room temperature at room

O”, stirred

and stlrred

of sodium

N2 atmosphere

6 0.91 (t,

3H),

1.20-1.85

(m, 3H), 4.9 (d, IH), 5.1 (m, IH). [al,

(m, 6H), 3.32-3.53

-160.5

k,

1.015,

(m, 4H), 3.82-3.95

methyl)-2,5-di&oxy-5-C_(n-propyi)-~~yxofur~Osi~-2,~-~

Methyl-2-C-(carboxymethylene

(m,

CHC13).

-lactone

(12): A mixture

of 10 (8-anomer,

0.060 g, 0.28 mmol)

mL, 5 mmol) In CH2C12 (5 mL) was heated and decanted.

Residue

orgamc

were

layers

was drssolved

washed

at reflux

m aq. NaHC03

sequentially

with

Cr03

(0.4 g, 4 mmol)

and pyrrdme

(0.4

for 3 h. It was cooled to room t-loperature

solutron

aq. NaHC03

and extracted solution,

water,

with CH2C12. Combmed 2N aq. HCI

and brme.

523

Synthesis of (-)-canadensolide

It

was filtered

by

column

a small

1H NMR(CDC13):

yield. (m,

through

2H),

5.57 (d, IH),

silica

gel

gel,

10%

6 0.80 (t,

3H),

1.10-1.25

6.22 (d, IH).

Residue

and evaporated.

EtOAc

in pet.

ether)

to

obtained

furrush

was purified

12 (0.04

g) m 74%

(m, 6H), 3.31 (s, 3H), 3.8-4.10 (m, 2H), 4.63-4.92 -1 1780 cm (CO). M+ 212. ti], -80.5 (c 0.745, CHC13).

IR(Neat):

methyl)-2,5-di&oxy-5-C&propyl)_Dlyxono-l,4-lactone-2,3-lactone

2-C_(Carboxymethylene

densolide)

pad of

(silica

chromatography

(cana-

(I):

MethodA Compound

10 (0.030

2 drops of cont. ture,

treated

with

HCI

with

ether.

Residue

was

filtered

dissolved washed

through

Method

solid

at

cation

(0.028

50%

with

aq.

Aqueous

(0.4

solution

and

mL)

contaming

and dried

and extracted

(Na2S04).

Solvent

yield.

g, 4 mmol)

and pyridme

(0.4

mL,

to room temperature

extracted

solution,

gel and evaporated

(2

was separated

water

3 h. It was cooled

aq. NaHC03

acid

was cooled to room tempera-

layer

aq. NaHC03,

Cr03

acetic

mixture

g) m quantitative

for

NaHC03

PDC

(0.3

of

with

water,

CH2C12.

a complex

5 mmol)

and decanted.

Combmed

2N aq. HCI

to give

ether

orgamc

and brine.

mixture

g) m 70%

yield.

It was

of products.

H-21,

(dt,

g) at

room

temperature

IH,

H-41,

0.92

5.18 (d, IH,

H-3),

and 1670 cm -1. M+ 124, i&l,

mmol)

a small pad of silica

(t,

3H),

6.14

-160 (c 0.1, CHC13.

gel,

(dq, IH, h],

extracted

dried

in CH2C12

for

treated

with

(Na2S04).

gel.

Evaporation

ether. Solvent

was treated

1.81-1.90

6.48 (dq,

mixture

of solvent

m pet. ether)

4H),

H-A),

(2 mL)

I h. The reaction

10% EtOAc

1.42 (m,

lit.3

and and

2 drops of cont.

temperature,

yield.

g, 0.150

6

water

g) in quantitative

(silica

to room

separated

0.032

by column chromatography 1H NMR(CDC131:

was

solution,

(13,

through

(2 mL) contammg

was cooled

layer

NaHC03

13 (0.032

lactol (0.020

and filtered

aq.

AcOH

mixture

Aqueous

water.

above

in 50% aq.

Reaction

washed

gl and NaOAc

of residue

4.69

and

the lactol

the

mmol)

30 mm.

were

to afford

solution

with

ether

layers

A

g, 0.168

60” for

NaHC03, ether

was evaporated

diluted

II

pad of silica

12 (0.038

heated

Combined

with

washed

g, 0.4 mmol),

aq.

m

B:

was

with

in

and water.

were

at reflux

sequentially

a small

Compound HCI

the lactol

of 11 (0.028

-anomer)

ether

layers

(5 mL) was heated

were

mmol,

at 60“ for 30 min. Reaction

NaHC03,

ether

to afford

A mixture in CH2C12

layers

solid

Combined

was evaporated

g, 0.14

was heated

(m, lH,

and purifi-

afforded 2H),

H-B).

was

4.05

I (0.022 (dt,

lR(Neat1:

IH, 1780

-162 (c 3.2, CHC13).

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e) G.

25,

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b)

J.H.

N. Taniguchi, d) A. M.

Hutchmson, K. Fukumoto

Srikrishna

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