Novel amidase catalysed process for the synthesis of vorinostat drug.

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 ) 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.