Synthesis of L-Ascorbyl Flurbiprofenate by Lipase-Catalyzed Esterification and Transesterification Reactions.

Jia-Ying Xin,Li-Rui Sun,Chun-Gu Xia,Yan Wang,Shu-Ming Chen

doi:10.1155/2017/5751262

Abstract

The synthesis of L-ascorbyl flurbiprofenate was achieved by esterification and transesterification in nonaqueous organic medium with Novozym 435 lipase as biocatalyst. The conversion was greatly influenced by the kinds of organic solvents, speed of agitation, catalyst loading amount, reaction time, and molar ratio of acyl donor to L-ascorbic acid. A series of solvents were investigated, and tert-butanol was found to be the most suitable from the standpoint of the substrate solubility and the conversion for both the esterification and transesterification. When flurbiprofen was used as acyl donor, 61.0% of L-ascorbic acid was converted against 46.4% in the presence of flurbiprofen methyl ester. The optimal conversion of L-ascorbic acid was obtained when the initial molar ratio of acyl donor to ascorbic acid was 5 : 1. kinetics parameters were solved by Lineweaver-Burk equation under nonsubstrate inhibition condition. Since transesterification has lower conversion, from the standpoint of productivity and the amount of steps required, esterification is a better method compared to transesterification.

Highlights

The treatment of Alzheimer’s disease is still a major challenge for the medical field
The present study focused on lipase-catalyzed synthesis of L-ascorbyl flurbiprofenate
Lipase-catalyzed acylation of L-ascorbic acid was performed in presence of racemic flurbiprofen or racemic flurbiprofen methyl ester

Summary

Introduction

The treatment of Alzheimer’s disease is still a major challenge for the medical field. The clinical failure of efficient Alzheimer’s disease drug delivery may be largely attributed to the low permeability of drugs due to the blood-brain barrier and a lack of appropriate drug delivery systems [1]. Localized and controlled delivery of drugs at their desired site of action can reduce toxicity and increase treatment efficiency. It has been reported that L-ascorbic acid could be used as a carrier to promote brain drug delivery [5,6,7]. To overcome the problems of the low blood-brain barrier permeability of flurbiprofen and to increase its delivery to the brain for the treatment of Alzheimer’s disease, one attractive approach is to design and synthesize flurbiprofen ester prodrug named L-ascorbyl flurbiprofenate containing ascorbate as a specific carrier system for brain delivery

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Conclusion