Enzymatic Removal of Carboxyl Protecting Groups. 1. Cleavage of the tert-Butyl Moiety

Abstract

[reaction: see text] A recent discovery that a certain amino acid motif (GGG(A)X-motif) in lipases and esterases determines their activity toward tertiary alcohols prompted us to investigate the use of these biocatalysts in the mild and selective removal of tert-butyl protecting groups in amino acid derivatives and related compounds. An esterase from Bacillus subtilis (BsubpNBE) and lipase A from Candida antarctica (CAL-A) were identified as the most active enzymes, which hydrolyzed a range of tert-butyl esters of protected amino acids (e.g., Boc-Tyr-O(t)Bu, Z-GABA-O(t)Bu, Fmoc-GABA-O(t)Bu) in good to high yields and left Boc, Z, and Fmoc-protecting groups intact.

Hydrolase‐Catalysed Preparation of Chiral α,α‐Disubstituted Cyanohydrin Acetates

“…This molecule differs from 1a only by a C C in the position of the nitrile group, indicating the importance of electronic effects for the enzyme activity. [7,10,11] The most notable result is the significant activity and selectivity of the protease Subtilisin A (SubA) for all substrates 1a-d. With an enantioselectivity as high as E = 58 for 1c, the stereoselectivity of this enzyme is remarkable. In addition, SubA displays (S)-enantioselectivity, the opposite to that of lipases CRL and BCL.…”

Prediction of the Candida antarctica Lipase A Protein Structure by Comparative Modeling and Site‐Directed Mutagenesis

“…The results from site-directed mutagenesis experiments strongly suggest that the catalytic triad consists of Ser184, His366, and Asp334 (Figure 4) In a recent paper by Schmidt et al [37] it was proposed that a GlyGlyGly-X or GlyGlyAla-X (where X is any amino acid) motif in the oxyanion hole enables CalA and other hydrolases to catalyze hydrolysis of tert-butyl alcohol esters. For CalA this sequence is GlyGlyAlaHis and occurs at positions 185-188 and is located next to the proposed catalytic serine 184.…”

Enzymes for the removal of N-carbobenzyloxy protecting groups from N-carbobenzyloxy-d- and l-amino acids

“…Boc, CBz etc.) are often used as protecting groups during enzymatic hydrolysis of other ester or amide groups in the compound [14][15][16][17][18][19].…”