P-49 Z選択的分子内Horner-Wadsworth-Emmons反応を用いた大環状ラクトンの合成(ポスター発表の部)

抄録

There are many bioactive macrolides containing Z-α,β-unsaturated lactone moiety such as macrolactin A, disctyostatin, phorboxazoles, and laulimalide. Although the intramolecular HWE reaction is one of the most reliable macroclization procedure, the reactions generaly give E-α,β-unsaturated olefines with high selectivity. Therefore, we decided to apply our Z-selective HWE reagents (ArO)_2P(O)CH_2CO_2R for the intramolecular HWE reaction and define the satisfactory reaction conditions. The substrates were prepared by the esterification of (ArO)_2P(O)CH_2CO_2H with the mono-THP protected diols, followed by deprotection and oxidation reaction. When the substrates having (o-t-BuPhO)_2P(O) moiety was added to a THF solution containing 3 eq. of NaH or NaI-DBU by using a syring pump, the intramolecular HWE reaction proceeded efficiently to give macrolactones in 94-99% Z selectivity with 60-99% yields. On the other hand, the substrate having (EtO)_2P(O) moiety was added to d CH_3CN solution containg 3 eq. of LiCl-DBU, the reaction give macrolactones in 89-100% E selectivity with 60-84% yields. [chemical formula]