Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives
Abstract Racemic cis ‐10‐azatetracyclo[7.2.0.1 2,6 .1 4,8 ]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200...
Published in: | Advanced Synthesis & Catalysis |
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Main Authors: | , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Wiley
2004
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Subjects: | |
Online Access: | http://dx.doi.org/10.1002/adsc.200303205 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fadsc.200303205 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.200303205 |
Summary: | Abstract Racemic cis ‐10‐azatetracyclo[7.2.0.1 2,6 .1 4,8 ]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200) N ‐acylation with 2,2,2‐trifluoroethyl butanoate afforded methyl (1 R ,4 R ,5 S ,8 S )‐5‐aminotricyclo[4.3.1.1 3,8 ]undecane‐4‐carboxylate and the (1 S ,4 S ,5 R ,8 R )‐butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β‐lactam to the corresponding N ‐hydroxymethyl‐β‐lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia ) lipase‐catalyzed enantioseletive O ‐acylation provided the (1 S ,4 S ,6 R ,9 R )‐alcohol (ee=87%) and the corresponding (1 R ,4 R ,6 S ,9 S )‐butanoate (ee>99%). In the latter method, competition for the enzyme between the (1 R ,4 R ,6 S ,9 S )‐butanoate, 2,2,2‐trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1 S ,4 S ,6 R ,9 R )‐alcohol with time. |
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