P-28 PP2A阻害活性天然物Phoslactomycin Bの全合成(ポスター発表の部)

概要

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Phoslactomycin B is a member of the phoslactomycin family of phosphate ester antibiotics (PLM) that display potent antitumor activity against a broad range of cancerous cell lines in vitro. Such antitumor activity is attributed to highly potent and selective inhibition of protein phosphatase 2A (PP2A). Their interesting molecular architectures and the potential as a lead compound for developing antitumor drugs make PLM attractive targets for synthesis. We describe here an efficient asymmetric synthesis of (+)-phoslactomycin B, which enables us to secure various analogues required for biological testing as well. Based on the methodology we have developed in the total synthesis of fostriecin, a congener of PLM, (+)-phoslactomycin B was synthesized by a highly enantio- and stereoselective approach involving asymmetric pentenylation for the introduction of C4 and C5 chiral centers, Suzuki-Miyaura coupling for the attachment of the characteristic C8 aminoethyl substituent, ring-closing metathesis for the construction of the δ-lactone moiety, Sharpless asymmetric dihydroxylation for the assembly of C8 and C9 hydroxy groups, and Stille coupling. The synthetic method developed enables us to synthesize three other isomers concerning the C11-OH and Δ^<12>-double bond.
天然有機化合物討論会の論文
2008-09-01