Enzymatic procedures for the synthesis of water-soluble retinol derivatives in organic media

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• 作者：Rejasse ; Barbara ; Maugard ; Thierry ; Legoy ; Marie Dominique
• 关键词：Retinoids ; Water-soluble retinols ; Candida antarctica ; Lipase ; Acylation
• 刊名：Enzyme and Microbial Technology
• 出版年：2003
• 出版时间：February 3, 2003
• 年：2003
• 卷：32
• 期：2
• 页码：312-320
• 全文大小：167 K

文摘

Vitamin A and its derivatives (retinoids) are of great commercial potential in cosmetics and pharmaceutical industries, for example, in skin care products. However, the clinical effectiveness of these retinoids is limited by skin irritation, water insolubility and extreme instability with the exception of retinyl esters. In this paper, we have prepared by an enzymatic process, non-ionic water-soluble analogues of retinol (Vitamin A alcohol). Two steps were necessary. In the first step, immobilised lipase from Candida antarctica (Novozym 435) was used in organic media to catalyse acylation of retinol by reverse hydrolysis, alcoholysis, acidolysis and inter-esterification with several bifunctional acylating agents. The influence of solvent, the molar ratio of substrates, the concentration of substrates, the temperature and the water activity (a_w) on enzymatic activity were examined in order to determine the optimum conditions of synthesis. The best results were obtained by acidolysis from 100mM retinyl palmitate and 500mM diacid (such as adipic acid), at 40°C, in dry tert-amyl alcohol. In these conditions, 73 % of retinyl palmitate was converted into retinyl adipate for only 9 % of retinyl palmitate hydrolysis. In second step, we reacted the activated retinol derivative such as retinyl adipate with different nucleophiles such as sugars and polyols in order to produce a non-ionic water-soluble retinol derivative. In the best conditions, 80 % of sorbityl retinyl adipate was obtained from retinyl adipate (7.5mM) and sorbitol (30mM) in dry tert-amyl alcohol.