Issue Italian-Swiss Medicinal Chemistry Meeting ARKIVOC 2006 (viii) 66-73
ISSN 1424-6376 Page 66
©
ARKAT
“One-pot” synthesis of 2-acetamido-2-deoxy-1,3,6-tri-O-acetyl-α-D-
glucopyranose as intermediate for N-acetyl-α-D-lactosamine
heptaacetate preparation
Marco Filice, Daniela Ubiali, Giuseppe Pagani, Marco Terreni,* and Massimo Pregnolato*
Pharmaceutical Biocatalysis Laboratories, Dipartimento di Chimica Farmaceutica, Via
Taramelli 12, Università degli Studi di Pavia, I-27100 Pavia, Italy
E-mail: markt@pbl.unipv.it , maxp@pbl.unipv.it
Abstract
We have recently reported the synthesis of different acyl pyranoses, bearing only one free
hydroxyl group, obtained by regioselective enzymatic hydrolysis of the peracetylated precursors
and subsequent acyl migration of the hydrolyzed products.
1
As a part of this ongoing research,
we have focused our attention onto the pure regioisomers of 2-acetamido-2-deoxy-1,3,4,6-tetra-
O-acetyl-α-D-glucopyranose (1) as key intermediate for the preparation of a large number of
oligosaccharides. Particularly, we have developed an efficient process to obtain a deprotected
derivative of 1 having only one free hydroxyl group at the C-4 position (3) as a valuable synthon
for the preparation of N-acetyl-α-D-lactosamine heptaacetate (4), building-block in a new
synthetic pathway for oligosaccharides like Sialyl Lewis
x
. Our chemo-enzymatic strategy allows
to obtain the disaccharide (4) in good overall yield, starting from a commercially available cheap
compound and without any intermediate purification. Our approach is, indeed, an interesting
alternative to the classical multi-step chemical procedures that are often plagued by low yields
and formation of undesired by-products.
Keywords: Carbohydrates, regioselective enzymatic hydrolysis, acyl group migration, N-acetyl-
α-D-lactosamine heptaacetate, Candida Rugosa lipase
Introduction
Oligosaccharides have recently received considerable attention because of their biological roles.
In fact, carbohydrates actively control a whole range of biological and pathological processes
e.g. immune-defense, viral replication, parasitic infections, cell-cell adhesion, cell-cell
recognition, etc.
2
This evidence provides further opportunities for the therapeutic treatment of
diseases, such as diabetes, AIDS and cancer, with new oligosaccharides. Particularly, the
challenge of developing carbohydrate-based anticancer vaccines is being actively sought. Tumor