Facile Synthesis of Sugar Lactols via Bromine-Mediated Oxidation of Thioglycosides.

Synthesis of a variety of sugar lactols (hemiacetals) has been accomplished in moderate to excellent yields by using bromine-mediated oxidation of thioglycosides. It was found that acetonitrile is the optimal solvent for this oxidation reaction. This approach involving bromine as oxidant is superior to that using N-bromosuccimide (NBS) which produces byproduct succinimide often difficult to separate from the lactol products.

Synthesis and antitumor activities of aquayamycin and analogues of derhodinosylurdamycin A.

Total syntheses of aquayamycin (3) and a number of analogues of angucycline antitumor antibiotic derhodinosylurdamycin A bearing various 2-deoxy sugar subunits (4-7) have been achieved. These molecules (3-7) were synthesized based on a convergent strategy for the synthesis of derhodinosylurdamycin A (2) previously reported from our group. In particular, our recently developed mild cationic gold-catalyzed glycosylation with S-but-3-ynyl thioglycoside donors was employed for the synthesis of analogues (6 and 7) bearing disaccharide subunits containing α-l-olivoside and α-l-olioside moiety, respectively. Aquayamycin (3), analogues (4-7), and our previously synthesized derhodinosylurdamycin A (2) were then submitted to the Development Therapeutics Program of the National Cancer Institute of National Institutes of Health for the NCI-60 Human Tumor Cell Lines Screening using standard protocols. It was found that derhodinosylurdamycin A (2), aquayamycin (3), and three other analogues (5-7) bearing sugar subunits did not show significant antiproliferative activity against those cancer cell lines. Interestingly, analogue (4) bearing no sugar subunit demonstrates good potential for growth inhibition and cytotoxic activity against a variety of human cancer cell lines.

Synthesis of S-linked trisaccharide glycal of derhodinosylurdamycin A: Discovery of alkyl thiocyanate as an efficient electrophile for stereoselective sulfenylation of 2-deoxy glycosyl lithium.

Stereoselective synthesis of S-linked trisaccharide glycal of angucycline antitumor antibiotic derhodinosylurdamycin A is described. The synthesis has been accomplished employing our previously reported umpolung S-glycosylation strategy - stereoselective sulfenylation of 2-deoxy glycosyl lithium. It was found that sugar-derived thiocyanate was a better electrophile than corresponding asymmetric disulfide in this type of stereoselective sulfenylation.