Asymmetric Total Synthesis of (−)-Laulimalide: Exploiting the Asymmetric Glycolate Alkylation Reaction
2002; American Chemical Society; Volume: 124; Issue: 21 Linguagem: Inglês
10.1021/ja026269v
ISSN1943-2984
AutoresMichael T. Crimmins, Matthew G. Stanton, Shawn P. Allwein,
Tópico(s)Asymmetric Synthesis and Catalysis
ResumoA 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 α,β-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.
Referência(s)