Premium
Thermodynamically Controlled Synthesis of Amide Bonds Catalyzed by Highly Organic Solvent‐Resistant Penicillin Acylase Derivatives
Author(s) -
Abian Olga,
Mateo César,
FernándezLorente Gloria,
Guisán José Manuel,
FernándezLafuente Roberto
Publication year - 2008
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp034266w
Subject(s) - chemistry , diglyme , yield (engineering) , penicillin amidase , amide , amine gas treating , acetic acid , derivative (finance) , ethanolamine , covalent bond , catalysis , organic chemistry , nucleophile , solvent , enzyme , immobilized enzyme , materials science , economics , financial economics , metallurgy
Abstract A study of various direct condensations between different amines, having very high pK values, and unmodified acyl donors has been performed. This has been possible by the use of a very stable PGA derivative. First, it has been found that the higher the cosolvent concentration, the higher the pK of the acyl donor and thus the higher the yield. Therefore, these high concentrations of cosolvents seem to be a requisite for certain enzymatic condensations. Using ethanolamine and 2‐hydroxy‐2‐phenylethyl‐amine as nucleophiles and phenyl acetic acid as the acyl donor, the increase in the diglyme concentration from 50 to 90% (v/v) permitted improvement of not only the yield (reaching values higher than 99% in both cases) but also the reaction rates (by 360‐ or 3‐fold, respectively). However, even when using PGA preparations stabilized by multipoint covalent attachment, it was not possible to obtain these results by inactivation of the enzyme derivative. Thus, in the protection of the octylamine with phenylacetic acid in 90% diglyme, the enzymatic activity was more than 20‐fold higher using the hydrophilized derivative than the glyoxyl PGA, which allowed us to obtain a yield higher than 99%. Thus, the use of hydrophilized derivatives that are very stable even in the presence of high concentrations of organic solvents opens new opportunities in the use of PGA in organic chemistry.