There has been much interest in the chemistry and biochemistry of the pseudo-oligosaccharidic a-D-glucosidase inhibitors* which contain common structural units composed of 4-amino-4-deoxy-or 4-amino-4,6-dideoxy-D-glucopyranose and saturated or unsaturated branched-chain cyclitols. Oligostatin, isolated from the fermentation broth of Sfreptomyces myxogenes nov. sp. SF-1130, is such an inhibitor and also has antibacterial activity 3. Methanolysis of oligostatin C (1) afforded a crystalline methyl a-glycoside (3, methyl dehydro-oligobiosaminide3 or acarviosin4). The formation of 3, instead of the expected core structure methyl oligobiosaminide (2), was rationalised in terms of an acid-catalysed dehydration involving the axial hydroxyl group of the inositol moiety, and 3 is five times more potent an a-D-glycosidase inhibitor than the parent pseudo-trisaccharide, acarbose4. Therefore, it is of interest to synthesise 2 and related compounds, and to study their biological properties. We now describe a synthesis of the protected derivative (15) of 2, and its 6-hydroxy analogue 11.
The condensation of methyl 4-amino-4-deoxy-5 (5) or 4-amino-4,6-dideoxy-a-D-glucopyranoside6 (7) with the 5,7-0-benzylidene derivative7 (8) of DL-3,4-di-Oacetyl-1,2-anhydro-(1,2,4,6/3,5) -1,2,3,4,5-pentahydroxy-6-hydroxymethylcyclohexane was envisaged as a route to a pseudo-disaccharide structure like 2. Hydrogenation of methyl 4-azido-6deoxy-cY-D-glucopyranoside5 (4) in methanol in the presence of Raney nickel T-48 gave 57% of 5. Treatment of 4 with sulfuryl chloride (2.5 mol) in pyridine at -10" gave 63% of the 6-chloro-6-deoxy derivative 6, hydrogenation of which in ethanol, in the presence of Raney nickel and potassium hydroxide, gave 92% of 7.
Condensation of molar equivalents of 5 and 8 in 2-propanol in a sealed tube *Synthesis of Pseudo-oligosaccharide Glycosidase Inhibitors, Part IV. For Part III, see ref. 12. For Part II and a preliminary report, see ref. 1.