Stereoselective Synthesis Of 1,2-cis-2-azido-2-deoxy Galactopyranosides

Aminoglycosides(2-amino-2-deoxy glycosides)which are widely distributed in organic organism are essent ial structural units of many active carbohydrates,such as aminoglycosides ant ibiot ics,heparin polysaccharides,glycoproteins of A-blood group antigens,etc.In recent years,the aminoglycoside has beco me an important target o f drug research and development due to its excellent bio logical act ivit ies.The stereoselect ive synthesis of aminoglycosides has gradually become a research focus in the field of carbohydrate chemistry,attract ing the attent ion o f many scho lars.Because o f the presence of 2-amino group,1,2-trans aminoglycosides(β-aminoglycosides)can be effect ively prepared through the participation of neighboring groups Co mparing with the synthesis of aminoglycosides has been reliable,there is no reliable strategy for the preparation o f α-aminoglycosides,especially for the α-2-amino-2-deoxy-galactosides.This pro ject aimed to develop a method of the stereoselect ive synthesis o fα-aminoglycosides.To avoid the interference of amino group on glycosylation,azide was used as the precursor of amino group.Firstly,1,2-cis-2-azido-2-deoxygalactose was prepared,and then azide was reduced to amino group t o afford1,2-cis-2-amino-2-deoxygalactosides.The stereo select ivit y o f the method arises fro m the co mbination o f a cyclic protect ing group together with a steric hindered protect ing group on the donor which make the acceptor mainly attack from the unimpede d side.2-azido-2-deoxygalactosylt hioglycoside donors 15 and 16 were designed to react with a secondary alcoho l 27 and a primary alcohol 28.The cyclic benzylidene group is installed at the C-4 and C-6 of the galactopyranosides and the steric-hindered silico n group was installed at the C-3 which can guide the α-glyconsidat ion.we find4,6-benzylidene-3-O-tert-but yldiphenylsilylprotected thiogalactosides were the most effect ive donors for the α-stereoselect ivit y.Then,the donor was glycosylated with a series of acceptors.It was found that thioglycan donor 16 had poor select ivit y fo r primary hydroxyl receptor but high stereoselectivit y for secondary hydroxyl receptor(α:β > 7:1,yield > 71 %).The reaction mechanism is inferred from the diffraction results o f thioglycoside donor 16 and the designed comparison experiment.Finally,in order to verify the practicabilit y of the method,branched pentasaccharide 77 on the surface o f Mycobacterium tuberculosis cells was synt hetised.The total yield was 20.4%.The structure of the product was confirmed by NMR and MS.