A concise synthesis of single‐enantiomer β‐lactams and β‐amino acids using Rhodococcus globerulus

Abstract

BACKGROUND: Pharmaceutical companies continue to evaluate β-amino acids and β-lactams in a range of drug candidates. The development of a highly efficient and selective bioresolution of cyclic β-lactam substrates could yield enantiopure lactams and β-amino acids with medicinal potential. The aim of this work was to discover and develop a biocatalyst capable of selectively hydrolysing β-lactam substrates.

Synthesis of Novel N-Heterocyclic Compounds Containing 1,2,3-Triazole Ring System via Domino, “Click” and RDA Reactions

“…133–134 °C, [α]D20 = +13 (c = 1, EtOH). 1 H and 13 C NMR data of the enantiomeric amino acids were identical with those of the racemic compounds [54,55,56,57,58,59].…”

Hydrolysis of Amides

“…In a screening of over 400 microbial strains for hydrolysis activity against the lactams 44 and 45, scientists at Chirotech Technology Ltd. identified two microorganisms with much higher b-lactamase activity than R. equi [149,150]. One of these novel biocatalysts, Rhodococcus globerulus NCIMB 41042, appeared to be highly enantioselective, and was used for the efficient resolution of the bi-/tricyclic lactams 44-47.…”

“…Both the residual b-lactam enantiomers and the corresponding b-amino acid products 48-51 were obtained in acceptable to excellent isolated yield and greater than 98% e.e. (E-ratio > 1000) (Scheme 15.9) [149][150][151]. Optimization of the bio-resolution of (AE)-6-azabicyclo[3.2.0]heptane-7-one (46) led to a process that can be operated at 60 g l À1 substrate concentration with a 20% wt/wt cell paste loading, which was successfully applied for the synthesis of multigram quantities of the enantiomerically pure b-lactam (1R,5S)-46 and b-amino acid (1S,2R)-50 [149].…”