Synthesis and partial biological evaluation of a small library of differentially-linked beta-C-disaccharides.
The synthesis of a small library of differentially-linked beta-C-disaccharides has been carried out through the use of a radical allylation-RCM strategy. Acids 6 were prepared by Keck allylation of a suitable carbohydrate-based radical precursor, followed by oxidative cleavage of the formed alkene. Dehydrative coupling of these acids with the known olefin alcohol 5 then gave the precursor esters 7 in excellent yield. Methylenation of the esters 7 was followed by RCM and in situ hydroboration-oxidation of the formed glycals to furnish the protected beta-C-disaccharides 10 in good overall yield. Five examples were then deprotected and screened for their efficacy as enzyme inhibitors of beta-glycosidase and against several solid-tumor cell lines for in vitro differential cytotoxicity.
Postema
Maarten H D
MH
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. mpostema@chem.wayne.edu
Piper
Jared L
JL
Liu
Lei
L
Shen
Jie
J
Faust
Marcus
M
Andreana
Peter
P
D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004187:Disaccharides / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D027861:Prunus / Q000737:chemistry*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
D004187:Disaccharides; D004791:Enzyme Inhibitors; D001617:beta-Glucosidase