Total synthesis of (+)-schweinfurthins B and E.
The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF(3).OEt(2). Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.
Topczewski
Joseph J
JJ
Department of Chemistry University of Iowa, Iowa City, Iowa 52242-1294, USA.
Neighbors
Jeffrey D
JD
Wiemer
David F
DF
D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001547:Benzaldehydes / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry; D001880:Boranes / Q000737:chemistry; D003500:Cyclization; D004852:Epoxy Compounds / Q000737:chemistry; D004987:Ethers / Q000737:chemistry; D008956:Models, Chemical; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis*
D000475:Alkenes; D000970:Antineoplastic Agents; D001547:Benzaldehydes; D001555:Benzene Derivatives; D016227:Benzoquinones; D001880:Boranes; D004852:Epoxy Compounds; D004987:Ethers; D013267:Stilbenes; C117233:schweinfurthin B; C545812:schweinfurthin E; C000928:dichlorodicyanobenzoquinone; C021274:boron trifluoride; C032175:benzaldehyde