Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives

• Published in: Advanced Synthesis & Catalysis
• Main Authors: Gyarmati, Zsuzsanna Cs., Liljeblad, Arto, Argay, Gyula, Kálmán, Alajos, Bernáth, Gábor, Kanerva, Liisa T.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2004
• Subjects: Antarc*; Antarctica
• 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

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.