Asymmetric Total Synthesis of (-)-Laulimalide: Exploiting the Asymmetric Glycolate Alkylation Reaction

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• 作者：Michael T. Crimmins ; Matthew G. Stanton ; and Shawn P. Allwein
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：May 29, 2002
• 年：2002
• 卷：124
• 期：21
• 页码：5958 - 5959
• 全文大小：43K
• 年卷期：v.124,no.21(May 29, 2002)
• ISSN：1520-5126

文摘

A concise total synthesis of the potent antitumor macrolide (-)-laulimalide is described. The observation that homoallylic (or latent homoallylic) C-O bonds are present at C5, C9, C15, C19, and C23 led to the strategic decision to rely heavily on the asymmetric glycolate alkylation to construct both the C1-C14 fragment 3 and the C15-C27 subunit 4. A diastereoselective addition of a C1-C14 allylstannane to a C15-C27 ges/gifchars/alpha.gif" BORDER=0>,ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-epoxyaldehyde served to join the two advanced fragments. A Mitsunobu macrolactonization of hydroxy acid 2 avoided isomerization of the sensitive 2,3-Z-enoate, which has been observed in base-catalyzed macrolactonizations. Removal of two TBS protecting groups to reveal the C15 and C20 hydroxyls occurred without rearrangement to isolaulimalide.