P-37 抗腫瘍性抗生物質PD113,271の合成研究(ポスター発表の部)

概要

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Fostriecin(1), along with two structurally related compounds PD113270(2), PD113271(3), are structurally unique and naturally-occurring phoshate monoesteres that exhibit potent and efficacious antitumor activity. It is known that these compounds inhibit DNA topoisomerase II and selectively inhibit protein phosphatase (PP) 2A and 4. The contribution, if any, that topoisomerase II versus PP2A/PP4 inhibition makes to their antitumor activity has not yet been fully defined. It is expected that molecular probe based on fostriecin will be a useful tool for elucidating the mechanism of the activity. We are making an effort on the total synthesis of PD113271 in order to determine its absolute configuration and to establish a practical synthetic route for the biological assay. The segment A (7) was synthesized from L-tartaric acid ester (Scheme 1), and the segment B (8) was synthesized from D-galactos (Scheme 2). At first, 7 was coupled with 8 by Horner-Emmons reaction to furnish the desired trans α,β-unsaturated ketone 14 (Scheme 3). Secondly, 14 was subsequently converted into (Z)-iodoalkene, the precursor of Stille coupling reaction. Then 18 was coupled with the segment C (6) by Stille coupling reaction. Finally, the introduction of phosphoester to 19 and subsequent global deprotection afforded (4S)-4-hydroxyfostriecin (Scheme 4).
天然有機化合物討論会の論文
2005-09-15