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Chemo‐ and Enantioselective Acyl Transfers by Lipases and Acylase I: Preparative Applications in Hydroxymethylpiperidine Chemistry
Author(s) -
Lundell Katri,
Lehtinen Petka,
Kanerva Liisa T.
Publication year - 2003
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200303018
Subject(s) - chemistry , candida antarctica , acylation , lipase , enantioselective synthesis , pseudomonas fluorescens , bifunctional , kinetic resolution , organic chemistry , piperidine , triacylglycerol lipase , enantiomeric excess , stereochemistry , catalysis , enzyme , biology , bacteria , genetics
The lipase‐ and acylase I‐catalysed acylation of bifunctional 2‐ and 3‐hydroxymethylpiperidines ( 1 and 2 ) and the alcoholysis of the corresponding diacylated counterparts 7 and 8 have been studied. Lipase AK from Pseudomonas fluorescens allowed the preparative‐scale resolution of 7 in neat butanol at 50% conversion whereas the 3‐regioisomer 8 reacted with negligible enantioselectivity (E=7). The lipase‐ and acylase I‐catalysed acylations of 1 and 2 in organic solvents proceeded with low enantioselectivity. On the other hand, more than 90% of 1 and 2 were transformed to amino esters 3 and 4 , respectively, in a highly chemoselective O ‐acylation with 2,2,2‐trifluoroethyl butanoate in the presence of Candida antarctica lipase A in TBME. The O ‐protected product 3 in the reaction mixture was readily available to another transformation at the piperidine nitrogen although 3 was not separated due to intramolecular O→N acyl migration. The tendency for acyl migration was much less significant in the case of 4 .