Abstract
The bleomycins are a family of glycopeptide antiumor antibiotics and exhibits potent biological activity via the metal-dependent oxidative cleavage of nucleotides in the presence of oxygen. Of all the bleomycin subunits the role of carbohydrate domain is the most poorly understand. Having adequate material with well-defined structure to study the interaction between glycopeptides and nucleotides is an urgent issue. A convenient route for the synthesis of disaccharide subunit is described here, including the development of new strategy in the preparation of unnatural L-ido and L-gulo sugars. 1,2:3,5-Di-O- isopropylidene-6-deoxy-a-D-xylo-hex-5-enofuranose 65 was obtained from commercially available diacetone a-D-gulose 63 in two steps and followed by stereoselective hydroboration of enol ether 65 to generate 1,2:3,5-di-O-isopropylidene-b-L-idofuranose 66. 3-O-benzyl-1,6- anhydro-b-L-gulopyranose 70 was preparated from L-idofuranose derivative 66 in three steps and followed by selective chiral center inversion at C2 provided 4-O-benzoyl-3-O- benzyl-1,6-anhydro-b-L-gulopyranose 72 as a glycosyl aceptor. The trichloroacetimidate 79 was generated from commercially available 2,3-O-isopropylidene-1,6-anhydro-b-D- mannopyranose 57 as a glycosyl donor in seven steps. Coupling of both donor and acceptor in the presence of TMSOTf led to the disaccharide 80 in 91% yield which underwent acetolysis to afford the desired the sugar moiety 81 in 95% yield.