Selective epimerization of rapamycin via a retroaldol/aldol mechanism mediated by titanium tetraisopropoxide

被引：19

作者：

Yang, W ^{[1
]}

Digits, CA ^{[1
]}

Hatada, M ^{[1
]}

Narula, S ^{[1
]}

Rozamus, LW ^{[1
]}

Huestis, CM ^{[1
]}

Wong, J ^{[1
]}

Dalgarno, D ^{[1
]}

Holt, DA ^{[1
]}

机构：

[1] ARIAD Gene Therapeut Inc, Cambridge, MA 02139 USA

来源：

ORGANIC LETTERS | 1999年 / 1卷 / 12期

关键词：

D O I：

10.1021/ol991209o

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] We describe the efficient and selective epimerization of the immunosuppressant rapamycin to 28-epirapamycin under mild conditions, The mechanism of epimerization involves an equilibrium of the four C28/C29 diastereomers through a two-step retroaldol/aldol (macrocycle ring-opening/ring-closing) sequence. This retroaldol/aldol equilibration is not restricted to rapamycin but is also applicable to acyclic beta-hydroxyketones, A potentially useful extension of this method-the use of beta-hydroxyketones as enolate synthons for effecting inter- or intramolecular aldol reactions under neutral conditions-is demonstrated.

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页码：2033 / 2035

页数：3

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