An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases

被引:50
作者
Campos, F [1 ]
Bosch, MP [1 ]
Guerrero, A [1 ]
机构
[1] CSIC, IIQAB, Dept Biol Organ Chem, ES-08034 Barcelona, Spain
关键词
D O I
10.1016/S0957-4166(00)00238-X
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
0The potent beta(2)-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2705 / 2717
页数:13
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