Synthesis of 1,5-dideoxy-1,5-imino-d-xylonolactam VIA acid-catalyzed intramolecular schmidt rearrangement

Tetrahedron

Pergamon

Leners.

Vol.

36. No. 43, pp 7811.7814,

1995 Elsevier Science Ltd Printed III Great Britain ca40-4039/95 59.50+0.00

0040.4039(95)01654-6

SYNTHESIS

OF

1,5-DIDEOXY-1,5-IMINO-D-XYLONOLACTAM INTRAMOLECULAR Peter

Department

SCHMIDT

Norris,

of Chemistry,

V/A

Derek

REARRANGEMENT

Horton’

and Brett

biological been

sugars,

carbohydrate

activities,

isolated

unnatural

most

from

imino

sugars,

as potential

treatments

diabetes5

We have

carbohydrate

Schmidt The

reaction

has been

available

by This

now

rearrangement exhibit

to afford

glycosidase

such as amidines.’ As a aldehydo

precluded reaction

because to afford

utility

Both been

of the furanose

expended methods.

and diseases

of sugar-derived

the

work

upon

of an (I)-azidodeoxy corresponding

3

pyranose

possess imino

synthesis

azides

for

the

interesting sugars

of both

examples

to carbohydrate

have

gained

preparation

have

natural

and

attention

metabolism,

derivative

a method

and

for

such

as

of a variety

by means

who

the

of

of an acid-

have

rearrangements natural-product Lewis

Sugar-derived

intermediates

in the

utility

shown

Schmidt

with

nitrogen-containing

synthetic

to various

aldehyde

derivative.

preparing

recently,

coworkers,

as a route

useful

and

Several

More

D-xylose-derived

1 and are

oxygen,

related

acid-catalyzed

recently

D-xylonolactam

properties.’

as

acid.’

of Aube

intramolecular9

expanded

N.W.

precursor.

employed

hydrazoic

ring

on the

of a D-xylono-1,5-lactam

been

with

mat

lactams

leads

have

and o We

to similar

been

of other

this are

of ketones ske1etons.t

acids

synthesis

of

lactams

shown

imino

to

sugars,

2 for (4 ) which

the

Schmidt

rearrangement

was expected

of D-xylose such

-D-xylose diethyl

5sulfonates

2.5-anhydro

we

to be accessible

azido-2,3,4-tri-Obenzoyl-5-deoxy-aldehydo 3, via activation

as HIV.4

classically

or

has been

precursor

-D-xylose

has

through

the

has

a new synthesis

expanded

inhibitory

in place

chemo-enzymatic

in me

substrate

treatment

effort

Ave.,

diethyl dithioacetal (3) undergoes etheratelHg0) to afford the unstable the trfbenzoate 6 of the title compound

of an a/dehydo5-azido-5deoxy-D-xylose

intermolecula@

that

and

interest

nitrogen

of glycosidases.’

much

infections

a ketone

methodology

found

viral

rearrangement

either

and

and now report

greatly

containing

inhibitors

by chemical

such

rearrangement

by treating

azides. have

both

a sustained

Schmidt

heterocycles

as

sources2

for

systems6

catalyzed

derivatives

notably

natural

Ft. Levine

The American University, 4400 Massachusetts Washington, D.C. 20016-8014, USA

Summary 5-Azido-2.3.4-tri-Obenzoyl-5-deoxy-D-xylose smooth Lewis acid-catalyzed demercaptalation (boron trifluoride aldebydoazide 4, which in the presence of Lewis acids yields ( 7 ) via an apparent intramolecular Schmidt rearrangement.

lmino

ACID-CATALYZED

dithioacetal (e.g.

sugars.

13

diethyl

as its 5sulfonic

me tosylate) A less-direct

in me xylo approach 7811

required

by means

dithioacetal ester

5azido-2,3,4-tri-Obenzoyl-5-deoxy-

of demercaptalatlon

and

series

of the corresponding

(3, scheme subsequent

are known

to 3 was therefore

1).

Access

displacement to undergo devised.

to the azide

with azide.

rapid

5-

Intramolecular

5-Azido-5-deoxy-

was

7812

1 ,2 -0isopropylldenea-D-xylofuranose crystalline

solid.

provided CHCl3),

the

(1 ). prepared’

Treatment

crystalline

of

diethyl

required

dithioacetal

659/o,

aldehydo

and

1 in 62%

into a syrupy

(3,

5-azido-5-deoxy

ethanethiol

dithioacetal

and this was converted

xylose

1 with

diethyl

[a]D

trifluoroacettc yield

tribenzoate, +15.8O.

sequence

4 by a four-step

acid

after

from

in chloroform

chromatography

identified

D-xylose, at

(mp

yielded room

1 as a

temperature

48-50°C,

[alo

+53.5’,

as 5-azido-2,3.4-triGbenzoyl-5-deoxy-D-

CHCl3).

which

Scheme

1

was expected

to be a suitable

precursor

to

the

derivative.

N3

CW3 1

Attempted only

according

of the desired

to the method

deoxy-aldehydo (190

ppm,

however hours

2

demercaptalation

low yields

of Vedejs,’

proved

a new

spectra

(‘H,

’ 3C, ‘H -‘l-l

COSY)l

CHCl3).

the

product

intramolecular

stereochemistry

of

of the alkene

prepared

to be unstable into

moeity

gave oil.

7 proved

good

this

(70-75%) NMR

It was found

isolated

compound

$tj!Q-elimination in 5 is considered

mercuric

of 4 all indicated

to be the of

4

(9.6

benzoic

carbonate oxide of ppm.

in aqueous and

TLC

1 t-f. CHO). aldehyde

a toluene on silica

a,&unsaturated acid

acetone,’

5 gave

trifluoride

etherate

5-azido-2.3,4-tri+benzoyl-5-

that refluxing

as shown

boron

singlet,

that the desired

by preparative

to be (n-

Scheme

3

yields proton

upon storage. compound,

and cadmium

of 3 with

Infrared.

sample

3

chloride

treatment

6 consistently

of a freshly

in conversion

mercuric

whereas

(4 ) as a colorless

spectra

the compound resulted

of 3, using

aldehyde,

-D-xylose CHO),

CH#3

between in scheme

solution gel. 5

C-2

C-3

and

2

5

1 3CNMR formed;

of 4 for

Analysis

aldehyde

3.

and

had been

([a]~ of

18

of NMR -12.60, 4

The

7813

Scheme

3

4

When FIT),

similar

varying

demercaptalation

amounts

crystalline

solid

identified

5

as

of a new.

(mp

178.18OOC.

2,3,4-t

intramolecular

intramolecular an exothermic

stirring

for

18

(NaOMe/MeOH) 7 lo),

4 into 6, carbon Schmidt

a freshly

h indeed

in eight

in line

tether

CHCl3)

formed.

which

over

an extended

Chromatography

on the basis (6 ),

and

g

evolution

provided

the

lactam

6

sample

of aldehyde

of spectral

product

of

and an

with that

from

D-xylose

proposed

the azide

by Aube

and carbonyl

4 was subjected

Thus,

treatment

of 4 with

TiClq

Allowing

me mixture

to gradually

(scheme

4).

isolated

in 84% (7)

in an overall

yield

et. al..g

IS outlined

functfonalities.

of time (16 h,

this

product

analytical

data,’

apparent

of 18%.

in dichloromethane

as

a

8 was

acid-catalyzed

warm

4.

known solution

as a colorless mechanism

These

authors

in 4, to be favorable

to effect at O°C

to RT and subsequent

Conventional

yield

A possible

in scheme

to conditions

yield.

in 80%

as is present

debenzoylation solid

(mp

68-

for the conversion suggest

of

that a four-

for ring-closure

via

rearrangement Scheme

BzOBao

NaOMe,

4

MeOH,

fOeo

6

This general

period

afforded

of gas.

1.5-dideoxy-1,5-imino-D-xylonolactam steps

between

prepared

rearrangement,

reaction

afforded

produced

+1.7O.

3 was conducted

were

rearrangement.g

Schmidt

caused

(u]b

dithioacetal product

r i Gbenzoyl-D-xylono-1.5-lactam

Schmidt

To test this hypothesis, the

of diethyl more-polar

reaction

synthetic

of azidodeoxy-aldebydo

utility,

for the

preparation

7

sugars of sugar

in the presence lactams.

of Lewis

acids

offers

a promising

mode,

of

7814

We gratefully

Acknowledgments:

(NIMH

and

Institutes Harold

NIDDK

of Health Shechter

References

acknowledge

respectively) (NIDDK)

for

help

for access

for helpful

with

Jack

Simpson

and Wesley

mass

spectra,

and

to a 300

discussions

MHz

NMR

Dr.

White

Schmidt

Yeh We

spectrometer.

on the acid-catalyzed

of the National

Herman

and

Institutes

June

Yun

are especially

of Health

of the

grateful

National

to Professor

rearrangement.

and Notes

1.

Legler,

2.

Fleet.

G.W.J..

3.

Look,

G.C..

4.

Jacob,

G., Adv.

Chem.

Winchester, Fotsch.

G.S..

Wong,

M.L..

National

B&hem.

1 9 9 0, 4 8.

B., Glycobiology

C.H..

Bryant,

208th

Papers

Carbohydr.

C.-H.,

Mueller,

Meeting

M.,

199.

1 9 9 2, 2.

Act.

319.

Chem. Res. 1 9 9 3, 26.

Schmidt,

M..

of The American

Dwek.

182.

R.A.,

Chemical

Platt,

Society,

F.M..

Butters,

T.D..

Washington,

D.C.,

August

Abstracts

of

1 9 9 4.

CARBlP. 5.

Liu, P.S.,

J. Org. Chem.

6.

a.

Baker.

D., Horton,

b.

El Khadem,

7.

Banthorpe,

4717

D., Carbohydr.

H.S..

D.V..

1 9 8 7, 52,

Horton,

1 9 7 0, 2 1. 393.

Res.

D., Meshreki,

in The Chemistry

M.H..

Carbonydr.

of the Azido

Group,

Res. 1 9 7 1, 16,

Patai.

S. (Ed,),

John

409.

Wiley

and Sons,

London,

1971,

221. 8.

Aube.

J., Milligan.

9.

AubB,

J., Milligan,

10.

Pearson,

W.H.,

abstracts

217.

11.

Fleet,

12.

a. Tong. b.

Boutellier,

Wolfrom.

M.L.,

16.

Vedejs,

E., Fuchs,

17.

Spectral

J.K.N.,

2 H). (m,

133.6, 1705,

Spectral

128.3,

W.A.,

71.9.

1635.

1 9 9 2, 5 7.

National

Organic

Symposium,

July

1995,

7.59-7.40

Hz, ‘66.9,

70.7. 460.

4 H), 4.2,

130.4, 1490,

H-4),

990,

45,

(m,

4 H),

319

Sot. 1 9 9 0, 7 7 2,

Schramm.

V.L..

Synlett.

6137.

1 9 9 5, 5,

510.

128.

1 9 6 5. 4 3,

129.2.

2345.

3.95

42.1;

Hz, 129.1.

(d,

366.

6 (CDC13)

69.2,

Hz,

53.6;

1 H, J 8.2.

5.7 Hz,

(m.

I H. J 4.3,

12.4

IR

165.2,

IR (CHCl3)

133.7, 3020.

H-3).

133.5, 1734,

6.08

8.11-8.02 (m,

1 H, J 7.3,

184.9,

(neat)

3057,

165.8. 2960,

4.2,

7.67-

4.2 Hz,

164.1,

149.1,

2928,

2843,

(m, 3 H),

7.44

2100,

M+.

8.06

Hz,

1 H),

(CDCl3)

365,

1 H NMR 6 (CDCl3)

(s, H-3),

13CNMR

(dd,

165.4,

9.45

1 H. J7.3

H-5,5’);

cm- I, MS (Cl. NH3)

8: 300 MHz 6.05

1H NMR 6.56

13.1

1260

165.6, 68.9,

B.A.,

1 9 7 1, 3 6,

5: 300 MHz (m.

1 H. N-H),

4.3

Tetrahedron1

B., J. Am. Chem.

Sot. 1 9 2 9, 5 7. 2188.

1 H. J 4.2, 131.0,

(CDCi3)

NH3)

8965.

34th

Res. 1 9 7 0. I 4,

P.L., J. Org. Chem.

1585,

(bs, 6.6.

D.R.,

Can. J. Charn.

data for compound

HL 6.24

Witty,

J. Am. Chem.

data for compound

1714,

(Cl,

N.G.,

D., Carbohydr.

Szarek,

134.2,

of Papers

B.. Horenstein,

Jones,

3.76

J. Org. Chem.

M.. Ganem,

15.

(m,

C.J.,

Abstracts

G., Ganem,

J., Horton,

H-4)

F.E.,

Papandreou,

14.

NMR

Mossman,

Ramsden.

M.K.,

Defaye,

J 5.7.

G.L.,

Sot. 1 9 9 1, 1 13.

218.

13.

18.

J. Am. Chem.

Lovering.

G.W.J.,

7.56

G.L.,

(m, 6 H), 7.57 5.78

H-5’).

(d.

3.67 133.4,

1687.

1 H, J 8.2 (m. 130.1,

1438.

M+l.

(Received in USA 6 July 1995; revised 22 August 1995; uccepted 23 August 1995)

Hz,

1 H, J 6.6,

1266,

129.9, 1220,

H-2), 12.4 129.8, 1094

(m,

5.64 Hz,

6 (m,

H-5);

128.5, cm-l,

1 H, 1% 128.4, MS