Novel amidase catalysed process for the synthesis of vorinostat drug

Abstract

Aim Presently, N‐hydroxy‐N′‐phenyloctanediamide (vorinostat) which is an effective histone deacetylase inhibitor, is being synthesized chemically. Hence, present study aims to develop an eco‐friendly approach for the synthesis of vorinostat from N′‐phenyloctanediamide through biotransformation. Methods and Results Using the amidase of Bacillus smithii IIIMB2907 in time course conversion and organic solvent compatibility, maximum bioconversion was observed at 12 h of reaction time and in presence of ethanol, respectively. Potassium phosphate buffer of pH 7·0 supported maximum bioconversion of N′‐phenyloctanediamide (10 mmol l−1) into N‐hydroxy‐N′‐ phenyloctanediamide at 40°C. Bench scale study was successfully carried out with 83% yield of purified vorinostat. Conclusion In this study, an eco‐friendly approach for the biotransformation of N′‐phenyloctanediamide into vorinostat was developed by using cell free extract of thermophilic strain B. smithii IIIMB2907. Significance and Impact of the Study Microbial amidase has achieved remarkable attention in the field of biotransformation for the green synthesis of hydroxamic acids. Utilization of amidase from B. smithii IIIMB2907, specifically in the synthesis of vorinostat drug is a foremost attempt in the development a novel process and can also be employed in the synthesis of its derivatives as well.

Enzymatic Catalysts for Hydroxamic Acid Formation: A Mini‐Review

“…Under optimized conditions, more than 90 % of N ′‐phenyloctanediamide was biotransformed into N ′‐hydroxy‐ N ′‐phenyloctanediamide with 83 % recovery yield of vorinostat (99.9 % purity HPLC). This was the first report of an amidase‐catalyzed process for vorinostat, a HDAC inhibitor 16. The addition of substituted side aromatic rings can provide the substrate scope for synthesizing derivatives of vorinostat.…”

“…Till 2020, only simple‐structured hydroxamic acids were reported and no complex structured hydroxamic acids were known due to the unavailability of a corresponding substrate for hydroxamic acid. However, for the first time, Singh and co‐workers reported the chemoenzymatic synthesis of vorinostat drug, a HDAC inhibitor through amidase enzyme 16. The present review summarizes the recent enzymatic developments in production approaches of hydroxamic acids with their potential applications in treatment of various diseases.…”

Probiotic characterization of Bacillus smithii: Research advances, concerns, and prospective trends

“…Acyltransferase B showed strong tolerance to many polar or nonpolar organic solvents, which also proved the potential for application in the synthesis of isohydroxamic acid (Agarwal & Choudhury, 2014). In 2020, the thermophilic amidase of B. smithii IIIMB2907 was used to synthesize the vorinostat drug ( N ‐hydroxy‐ N ′‐phenyl‐octanediamide), an environmentally friendly approach and a new attempt (Singh et al., 2020). Even more, it was found that the addition of Ɛ‐caprolactam to mineral‐based media induced the production of amidase in B. smithii (optimum temperature of 50°C and optimum pH of 7.0).…”