•First synthesis of S-linked trisaccharide glycal of derhodinosylurdamycin A.•Stereoselective construction of S-linked 2-deoxyglycosides via umpolung S-glycosylation.•Discovery of a sugar-derived thiocyanate as a better electrophile than its asymmetric disulfide counterpart.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.Download high-res image (117KB)Download full-size image

•Concise synthesis of the 2-deoxy trisaccharide glycal has been accomplished.•Stereoselective construction of 2-deoxy β-disaccharide is achieved via anomeric O-alkylation.•A concomitant debenzylation and elimination strategy is utilized for the synthesis of glycal.Synthesis of the 2-deoxy trisaccharide glycal of antitumor antibiotics landomycins A and E has been described. The synthesis involves an anomeric O-alkylation for the synthesis of 2-deoxy β-linked disaccharide, a tert-butyldimethylsilyl triflate-catalyzed α-selective L-rhodinosylation, and a lithium 4,4′-di-tert-butylbiphenyl-mediated reductive debenzylation and concomitant reductive lithiation-elimination for the production of the 2-deoxy trisaccharide glycal.

Stereoselective synthesis of carbohydrate mimics resistant toward acid-mediated or enzymatic hydrolysis is chemically challenging and biologically interesting. In this Letter, the first stereoselective synthesis of a “non-hydrolyzable” S-linked hexasaccharide of antitumor antibiotic landomycin A is described. This synthesis was accomplished through the utilization of our recently developed umpolung reactivity-based S-glycosylation–sulfenylation of stereochemically defined glycosyl lithium species with asymmetric sugar-derived disulfides.

An approach for direct synthesis of biologically significant 2-deoxy-β-glycosides has been developed via O-alkylation of a variety of 2-deoxy-sugar-derived anomeric alkoxides using challenging secondary triflates as electrophiles. It was found a free hydroxyl group at C3 of the 2-deoxy-sugar-derived lactols is required in order to achieve synthetically efficient yields. This method has also been applied to the convergent synthesis of a 2-deoxy-β-tetrasaccharide.

A mild and atom-economic gold(I)-catalyzed glycosylation for stereoselective synthesis of 2-deoxy α-glycosides using bench-stable 2-deoxy S-But-3-ynyl thioglycoside donors has been described. Under optimal conditions, 2-deoxy and 2,6-dideoxy thioglycoside donors were able to react with a variety of primary, secondary, and tertiary alcohol acceptors to afford α-selective glycosides in good to excellent yields.Keywords: 2-deoxy glycosides; alkyne; glycosylation; gold; homogeneous catalysis

Iodothiophene diacetates react with allyltrimethylsilanes in the presence of boron trifluoride diethyl etherate to afford corresponding ortho-allyliodothiophenes via reductive iodonio-Claisen rearrangement. This method has been successfully applied to the synthesis of Plavix®, a blood clot inhibitor used to reduce the risk of heart attack and stroke.

A mild and atom-economic rhenium(V)-catalyzed stereoselective synthesis of β-d-digitoxosides from 6-deoxy-d-allals has been described. This β-selective glycosylation was achieved probably because of the formation of corresponding α-digitoxosides disfavored by 1,3-diaxial interaction. In addition, this method has been successfully applied to the synthesis of digitoxin trisaccharide glycal for the direct synthesis of digitoxin and C1′-epi-digitoxin.