Lipase-catalyzed kinetic resolution of racemic 1-heteroarylethanols—experimental and QM/MM study

详细信息    查看全文

• 作者：Monica Toş ; a ; Sarolta Pilb&#xe1 ; k ; Paula Moldovan ; Csaba Paizs ; G&#xe1 ; bor Szatzker ; Gyö ; rgy Szak&#xe1 ; cs ; Lajos Nov&#xe1 ; k ; Florin-Dan Irimie ; L&#xe1 ; szló ; Poppe
• 刊名：Tetrahedron: Asymmetry
• 出版年：2008
• 出版时间：8 August 2008
• 年：2008
• 卷：19
• 期：15
• 页码：1844-1852
• 全文大小：533 K

文摘

The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a–d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a–d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g**)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a–d, four possible tetrahedral intermediate states were compared and analyzed.