Chemo‐ and Enantioselective Acyl Transfers by Lipases and Acylase I: Preparative Applications in Hydroxymethylpiperidine Chemistry
Abstract 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 nea...
| Published in: | Advanced Synthesis & Catalysis |
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| Main Authors: | , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2003
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1002/adsc.200303018 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fadsc.200303018 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.200303018 |
| Summary: | Abstract 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 . |
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