Design and synthesis of new 1,4-diaminocyclitol aminoglycosides: use of maltose as the key starting material

Abstract

New antimicrobial aminoglycosides having a pseudodisaccharide structure, 1L-(1,6/2,3)-3-amino-2-(2,6-diamino-2,6-dideoxy-α-D-allopyranosyloxy)-6-[glycyl(methyl)amino]cyclohexanol (4) and its 3′-deoxy analogue (5) have been synthesized from 1,6-anhydro-β-maltose (6), utilizing its internal glycosidic linkage. This synthesis involves regio- and stereo-selective introduction of amino precursors, azido and methylamino groups, and transformation of the 1,6-anhydrohexopyranose moiety into a cyclitol moiety. The latter was accomplished by application of novel chemical devices, such as formation of phenyl 1-thioglycosides (32) and (39) by selective fission of 1,6-anhydro rings of disaccharides, and application of Ferrier's carbocyclization reaction to the thioglycosides.