SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 415

an advantage in terms of -selectivity and especially yield compared to the corre-

spondingmono- N -acetyl glycosyl compounds. For example, sialylation of acceptor B
gave the disaccharide in 98% yield and good a -selectivity ( a / b ¼ 2.5:1), whereas use
of the mono N -acetyl congener gave only 67% of the corresponding disaccharide and
a

a

/ selectivity of 2:1 [110].

a b

12.5.1.3. -Sialylation by Participation of a C1 Group Several approaches

have been investigated making use of stereodirecting auxiliaries at C1 of the sialyl
donor. Perhaps the most promising of these comes from Kajihara and co-
workers [111], who developed sialyl donors in which stabilization of glycosyl
oxocarbenium is achieved by an amide residue (Scheme 12.36) and applied their
strategy to the synthesis of sialyl-T N -MUC4 glycopeptide, a potential immune
response target [112]. Of the two different three-membered ring intermediates
possible, one is favored and gives rise to

a

-selectivity. Use of a dimethylamide

a

was predicted to deliver -anomer.

In a similar vein, Takahashi and coworkers employed a methylthioethylester of
a Neu5Ac thioglycoside (Scheme 12.37) [113]. The activation of this donor gave an
oxocarbenium ion intermediate that was expected to be stabilized by long-range
participation of the thiomethyl moiety resulting in the formation of a sulfonium
intermediate. The axial sulfonium is apparently preferred and nucleophilic attack
gives the equatorial glycosylation, permitting the synthesis of a water-soluble taxol
analogue [113]. A related approach was subsequently developed by Haberman and
Gin [114].

b

OAc OAc

CONHMe

OAc OAc

OH

OP(OEt) 2
CONHMe

OH AcO

O

steps

TMSOTf, CH 2 Cl 2 AcHN

O
N 3

Sialyl-T N -MUC4
glycopeptide

O

AcO O AcO OH

OTE

AcO

AcHN -78 to -40°C

92%

O
N 3

AcO

OTE

AcO

(TE = CH 2 CH 2 TMS) ( α/β = 5.4:1)

OAc OAc OAc OAc

O

ROH

NHMe

AcO O AcO

O

NHMe

AcHN AcHN

AcO AcO

ROH

O

SCHEME 12.36

Synthesis of a sialyl-T N -MUC4 glycopeptide via participation from C1.

OAc

CO 2 CH 2 CH 2 SMe

OAc

OAc CO 2 CH 2 CH 2 SMe

AcO OAc

NIS, TfOH, DME

O AcO

O

SMe

+ HO N 3 O

AcHN O

2 N 3

AcHN O

-40 to 0°C
45%

2

AcO

AcO

O

steps

ROH

OH

OAc OAc CO 2 H

O

O S

OH

OAc OAc HO

AcO AcO O

O O

O S O O O N

H

AcHN Taxol

2

AcHN AcHN

HO

AcO AcO

ROH

SCHEME 12.37 Sulfide participation from C1 in the synthesis of Neu5Ac derivatives.