Concise stereocontrolled routes to fumagillol, fumagillin, and TNP-470.
A concise, diastereoselective synthesis of (+/-)-fumagillol (3) and formal, enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1) and TNP-470 (2) are reported. The origin of asymmetry is a highly diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone auxiliary. The stereochemical course of a key conjugate addition reaction is controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation.
Vosburg
David A
DA
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Weiler
Sven
S
Sorensen
Erik J
EJ
D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis*; D008968:Molecular Conformation; D015394:Molecular Structure; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C057299:fumagillol; C026211:fumagillin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol