通过α-苄氧基甲基酮羟醛策略合成peloruside A的C(1)-C(12)片段。

Synthesis of the C(1)-C(12) segment of peloruside A by an alpha-benzyloxymethyl ketone aldol strategy.

作者信息

Engers Darren W, Bassindale Martin J, Pagenkopf Brian L

机构信息

Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Org Lett. 2004 Mar 4;6(5):663-6. doi: 10.1021/ol036393z.

DOI:10.1021/ol036393z

PMID:14986944

Abstract

The C(1)-C(12) segment of 16-membered antitumor macrolide peloruside A has been prepared by a BF(3).OEt(2)-catalyzed Mukaiyama aldol reaction between a glucose-derived C(1)-C(7) aldehyde and a C(8)-C(12) alpha-benzyloxymethyl ketone. Exclusive 2,3-anti and moderate 3,5-anti/syn facial selectivity (3.5:1) was observed in the aldol reaction. The key C(1)-C(7) aldehyde contains the required stereochemistry at carbons two, three, and five, and has been efficiently prepared on multigram scales from commercial triacetyl D-glucal. [reaction: see text]

摘要

通过BF₃·OEt₂催化的葡萄糖衍生的C(1)-C(7)醛与C(8)-C(12)α-苄氧基甲基酮之间的Mukaiyama羟醛反应，制备了16元抗肿瘤大环内酯类化合物peloruside A的C(1)-C(12)片段。在羟醛反应中观察到了专一的2,3-反式和面选择性以及适度的3,5-反式/顺式面选择性（3.5:1）。关键的C(1)-C(7)醛在碳2、3和5处具有所需的立体化学结构，并且已经从商业三乙酰基D-葡糖醛高效地制备出了多克规模的产物。[反应：见正文]