A short enantioselective total synthesis of dammarenediol II
A short enantioselective total synthesis of dammarenediol II
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DOI：
10.1021/ja9620806
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发表时间：
1996-09-11
影响因子：
15
通讯作者：
Lin, SZ
中科院分区：
文献类型：
--
作者：
Corey, EJ;Lin, SZ
We report herein an enantioselective and unusually short synthesis of dammarenediol II (1), the primary product of the tetracyclization of (S)-2, 3-oxidosqualene in plants, 1, 2 and the plant analog of the mammalian sterol precursor protosterol, 3 hitherto a classical unsolved synthetic problem. Dammarenediol II is of considerable biosynthetic interest because of recent progress in the cloning of various (S)-2, 3-oxidosqualene cyclase genes and related bioorganic studies. 4 In addition, dammarenediol has been found to have antiviral activity against herpes simplex. 5 The sequence which we have developed for the first total synthesis6 of 1 is summarized in Scheme 1. The element of enantiocontrol in the synthesis was based on the recent development of a mechanistically designed biscinchona alkaloid catalyst for the terminal dihydroxylation of E, E-farnesyl acetate with> 120: 1 position selectivity and 98: 2 enantioselectivity to form diol 2 in 80% yield. 7 This key chiral intermediate was converted in 95% yield to (10S)-10, 11-oxidofarnesol (3) 7 by selective mesylation of the 10-hydroxyl (1.5 equiv of methanesulfonyl chloride and 10 equiv of pyridine in CH2Cl2 at 23 C for 12 h) and treatment with potassium carbonate in methanol at 23 C for 6 h. Epoxy bromide 4 was prepared from 3 in a one-flask process consisting of primary mesylate formation (CH3SO2Cl, Et3N, THF,-45 C for 30 min) and further reaction with LiBr in THF solution at 0 C for 2 h. The next phase of the synthetic plan required the stereoselective elaboration of the chiral epoxy bromide 4 to Z-tetrasubstituted silyl enol ether 8. Although there was no strong precedent for this task, the problem was solved in the following way. Acetyl-tert-butyldimethylsilane8 and 2-amino-1-methoxypropane (Aldrich) were heated at reflux in benzene with continuous removal of water to give the corresponding imine 5, bp 60-65 C at 1.5 Torr (85%). Deprotonation of 5 with 1.05 equiv of lithium diisopropylamide (LDA) in THF at-30 C initially and then at 0 C for 30 min afforded the corresponding lithium azaenolate (as a yellow solution) which was cooled to-30 C and treated with epoxy bromide 4 (at
