Abstract
Ceramides are sphingolipid compounds that are very attractive as active components in both the pharmaceutical and the cosmetic industries. In this study, the synthesis of 1- O ,3- N -diacyl 3-amino-1,2-propanediol-type pseudo-ceramides was developed at the semi-pilot scale, starting from a two-step continuous enzymatic process with immobilized Candida antarctica lipase B (Novozym ® 435) in a packed-bed bioreactor, previously optimized at the laboratory scale. This process involved the selective N -acylation of 3-amino-1,2-propanediol (step 1), followed by the selective O -acylation of the N -acyl 3-amino-1,2-propanediol synthesized in the first step, with various fatty acids as acyl donors, to produce N , O -diacyl 3-amino-1,2-propanediol-type pseudo-ceramides (step 2). Under partially optimized operating conditions, high synthesis yields and production rates were obtained, within the ranges 76–92% and 3.7–4.6 g h −1 (step 1), or 23–36% and 1–1.4 g h −1 (step 2), respectively, depending on the fatty acids used as acyl donors. The overall synthesis yields varied from 20 to 33%: the best yield was obtained using palmitic acid and lauric acid as first and second acyl donors, respectively. Together with the high production rates also obtained with these acyl donors, this confirms that this two-step process has great potential for the production of differently functionalized 1- O ,3- N -diacyl 3-amino-1,2-propanediol-type pseudo-ceramides on an industrial scale.
Highlights
Ceramides are natural compounds derived from the N-acylation of sphingosine and are key intermediates in the biosynthesis of all complex sphingolipids
The use of continuous-flow technology involving packed-bed bioreactors has become in recent years an innovative, promising and attractive alternative for the highly selective production of pure chemical compounds, providing several advantages: control and automatic operating, reduced costs, significant enhancement in the productivity of the biocatalyst and improvement in quality and yield (Chang et al, 2007; H-Kittikun et al, 2008). Starting from this overview, we previously developed an efficient process for the continuous enzymatic production of 1-O,3-N-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides using a packed-bed bioreactor containing immobilized Candida antarctica lipase B (Novozym 435) (Le Joubioux et al, 2014)
The continuous enzymatic synthesis of 1-O,3-N-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides catalyzed by immobilized C. antarctica lipase B (Novozym 435) was conducted in a semi-pilot scaled-up packed-bed bioreactor system (Scheme 1) in two steps, according to the process previously developed at the laboratory scale (Le Joubioux et al, 2014)
Summary
Ceramides are natural compounds derived from the N-acylation of sphingosine and are key intermediates in the biosynthesis of all complex sphingolipids Due to their major role in preserving the water-retaining properties of the epidermis (Coderch et al, 2003), ceramides and their analogs have a wide range of commercial applications, as active ingredients for the cosmetic industry, included in hair and skin care products, or for dermatological therapies: they are effective in restoring the water content of dry skin and in relieving atopic eczema (Kerscher et al, 1991). All these compounds are presently synthesized by chemical procedures, which involve several drawbacks: the need of fastidious steps of alcohol group protection and deprotection for the control of selectivity, as well as high temperatures that may preclude the use of fragile molecules and may cause coloration of the end products; the coproduction of salts and the use of toxic solvents (dimethylformamide, methanol, etc.) (Cho et al, 1995; Ha et al, 2006; Philippe and Semeria, 1998; Smeets and Weber, 1997)
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