Method for synthesizing ceramide-type compounds
View Patent ↗The invention relates to the fields of fatty substance chemistry, specifically of the ceramide-type compound synthesis. The invention resides substantially in the synthesis of ceramide-type compounds. Specifically, the aim of the invention is a new enzymatic synthesis method, comprising at least one amidification step and one esterification step, achieved through lipases, among fatty acids and/or esters thereof and amino alcohols. The resulting ceramide-type compounds can be used as cosmetic and/or pharmaceutical compositions, in particular as dermatological compositions in conjunction or in admixture with one or more suitable cosmetic and/or pharmaceutical excipients or carriers. The method has an interest particularly in the synthesis of active compounds useful in the fields of cosmetology and/or pharmacology and specifically of dermatology.
1. A process for the synthesis of a ceramide-type of the formula
wherein Am-Alc is alkyl of 2 to 6 carbon atoms derived from an amino alcohol, X is hydrogen or alkyl of 1 to 4 carbon atoms optionally hydroxylated in the 2′ position and AG and AG′ are individually unsaturated or saturated hydrocarbon of 4 to 30 carbon atoms derived from a fatty acid or fatty acid amide comprising reacting on amino alcohol of the formula
AmAlcOH
with an acid of the formula AG-COOH wherein AG is defined as above in the presence of a lipase B-type enzyme of Candida antarctica to introduce the
group and with an AG′-COOH wherein AG′ is defined as above in the presence of Rhizomucor miehei lipase to introduce the
group.
2. The process of claim 1 , wherein the amide formation step is carried out under stoechiometric conditions between the fatty acid or the amino-alcohol at a temperature comprised of 40 to 100° C.
3. The process of claim 1 , wherein the amide formation is carried out without solvent at a temperature of about 65° C.
4. The process of claim 1 , wherein the amide formation is carried out under a reduced pressure of 1 to 500 mbars during at least 16 hours.
5. The process of claim 1 , wherein the esterification reaction is carried out with a ratio fatty acid to amino-alcohol of 1 to 2.
6. The process of claim 1 , wherein the esterification reaction is carried out at a temperature of 40 to 90° C.
7. The process of claim 1 , wherein the esterification reaction is carried out without solvent at a temperature of about 65° C.
8. The process of claim 1 , wherein the esterification reaction is carried out under a reduced pressure of 1 to 500 mbars during at least 18 hours.
9. The process of claim 1 , wherein the enzymes used in each step are immobilized on an inert support.
10. The process of claim 1 , wherein the amide formation reaction with the Candida antartica lipase B and the esterification reaction with Rhizomucor miehei lipase are both carried out without solvent, optionally simultaneously, at a temperature of about 65° C. and under a reduced pressure of 30 to 200 mbars.
11. The process of claim 1 , wherein the starting amino-alcohol corresponds to formula:
in which:
n is 1, 2 or 3 and m is 1, 2 or 3,
X is hydrogen or C1 to C4 carbon chain, optionally hydroxylated on the positions 2′ and/or followings of the amino group;
R 1 is hydrogen or alkyl of 1 to 4 carbon atoms optionally hydroxylated,
R 2 is selected from the group consisting of hydrogen, —OH, —NH 2 and alkyl of 1 to 4 carbon atoms, optionally hydroxylated,
R 3 is selected from the group consisting of hydrogen, —OH and —CH 2 OH, in which at least one of R 1 , R 2 or R 3 includes a —OH.
12. The process of claim 1 wherein the amide formation step is performed before the esterification step.