Chemoenzymatic preparation of enantiopure homoadamantyl β-amino acid and β-lactam derivatives

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 P-lactam to the corresponding P-amino ester followed by Candida antarctica lipase A-cat-alyzed enantioselective (E> >200) N-acylation with 2,2,2-trifluoroethyl butanoate afforded methyl (IR,4R,5S,8S)-5-aminotricyclo[4.3.1.1(3,8)]undecane-4- carboxylate and the (1S,4S,5R,8R)-butanamide with >99% ee at 50% conversion. Alternatively, transformation of the P-lactam to the corresponding N-hydroxymethyl-beta-lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) li-pase-catalyzed enantioseletive O-acylation provided the (1S,4S,6R,9R)-alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)-butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)-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 (1S,4S,6R,9R)-alcohol with time.