FR2689132A1 - Enzymatic prepn. of methyl gluco-pyranoside mono:ester(s) in position 6 - is sample, gives good yields and avoids purificn. by chromatography - Google Patents

Abstract

Prepn., by an enzymatic route of monoesters in position 6 of methylglucopyranoside of formula (I) comprises reaction of methyl alpha-D-glucopyranoside with either (a) a fatty acid triglyceride of formula (II) or (b) fatty acid trifluoroethanolic ester (R-C(=O)-)-CH2-CF3), in the presence of a lipase. R = 6-21C alkyl or alkjenyl or a defined mixt. of these. USE/ADVANTAGE - Esters in position 6 of methyl glucopyranoside are potentially useful nonionic surfactants in the cosmetic, pharmaceutical and foodstuff industries, but it has not been possible to obtain sufficiently pure prods. by a simple and economic route. The enzymatic prepn. of prior art (WO9009451) still requires purifcn. of the prod. by chromatography. Use of (a) or (b) (above) instead of a fatty acid or lower alkyl fatty acid ester avoids this inconvenience and gives good yields (50-75 wt.percent)

Description

 The present invention relates to a new process for the enzymatic preparation of monoesters in position 6 of methyl glucopyranoside.

 The esters in position 6 of methyl glucopyranoside are known compounds which have in particular found use as nonionic surfactants in the cosmetic, pharmaceutical and food fields.

As regards more particularly the cosmetic field, there may be mentioned the articles by A. Seldner, Cosmet. and Toilet. 93 (3), 73-75, 1978 and NB Desai, Cosmet. and
Toilet. 105 (2), 99-107, 1990 as well as US patent 4,364,930.

 However, the interest of these compounds has hitherto come up against their obtaining in so far as the syntheses do not always make it possible to obtain sufficiently pure products in a simple and economical manner.

 Very recently, there has been proposed, in patent application WO 90/09451, a process for the enzymatic preparation of esters of various methyl glucosides, this process consisting in reacting a fatty acid or a lower allyl ester of such an acid with a glucoside in the presence of an enzymatic catalyst, more particularly, a lipase, esterase or protease.

 This process, if it has made it possible to provide better selectivity, however has the drawback of necessarily involving a purification step by chromatography, which makes its implementation particularly cumbersome and therefore, the interest.

 After various studies, it was unexpectedly and surprisingly found that it was possible to remedy the drawbacks of the state of the art as represented by patent application WO 90/09451 by carrying out the reaction not from a fatty acid or a lower allyl ester of fatty acid but using either a fatty acid triglyceride or a tritluoroethanolic fatty acid ester.

 The process according to the invention using a fatty acid triglyceride has the advantage of using a natural precursor of fatty acids and of not carrying out any reaction requiring activation, which leads to a particularly economical preparation method and fast with good yields.

 The process using a tritluoroethanolic fatty acid ester surprisingly leads to high yields, while it is well known that the fluorinated derivatives involved in an enzymatic reaction often cause inhibition of the enzyme.

 Thanks to the process according to the invention which will be described below in more detail, it is thus possible to selectively access the monoesters in position 6 of the methyl glucopyranoside under simple and rapid processing conditions and with yields high, of the order of 50 to 75%.

dans laquelle:
R représente un radical allyle, linéaire ou ramifié, ou alcényle ayant de 6 à 21 atomes de carbone ou R représente un mélange défini de tels radicaux alkyles ou alcényles, ce procédé consistant à faire réagir sur l'a-D-glucopyranoside de méthyle, soit un triglycéride d'acide gras de formule:

soit un ester tritluoroéthanolique d'acide gras de formule:

dans lesquelles le radical R a la même signification que ci-dessus, la réaction étant effectuée en présence d'une lipase, et éventuellement en milieu solvant organique.The present invention therefore relates to a process for the enzymatic preparation of monoesters in position 6 of methyl glucopyranoside having the following general formula:

in which:
R represents an allyl radical, linear or branched, or alkenyl having from 6 to 21 carbon atoms or R represents a defined mixture of such alkyl or alkenyl radicals, this process consisting in reacting with methyl α-D-glucopyranoside, or a fatty acid triglyceride of formula:

or a tritluoroethanolic fatty acid ester of formula:

in which the radical R has the same meaning as above, the reaction being carried out in the presence of a lipase, and optionally in an organic solvent medium.

 As the reaction organic solvent, it is preferred, according to the invention, to use pyridine, although other solvents may be used.

 The reaction temperature of the process is generally between 35 and 500C and the reaction time between 20 and 50 hours.

 The proportion in moles of fatty acid triglyceride relative to methyl glucopyranoside is generally between 5 and 0.5.

 The proportion in moles of the trifluoroethanolic fatty acid ester, relative to methyl glucopyranoside is generally between 5 and 0.5.

 According to the invention, the weight ratio of lipase relative to methyl glucopyranoside is approximately 3.

 Among the triglycerides which can be used according to the invention, mention may be made of the triglycerides of heptanoic, octanoic, nonanoic, decanoic, dodecanoic and hexadecanoic acids.

 It is also possible to use according to the invention products rich in triglycerides of defined structure such as natural oils such as olive oil.

 The trifluoroethanol esters are preferably chosen from those of heptanoic, octanoic, nonanoic, decanoic, dodecanoic and hexadecanoic acids.

 The lipase is preferably the pig pancreas lipase, but other lipases can also be used according to the invention.

GENERAL PROCESS FOR THE PREPARATION OF MONOESTERS IN POSITION 6 OF
METHYL a-D-GLUCOPYRANOSIDE
50 mmol of methyl a-D-glucopyranoside are dissolved in 100 ml of anhydrous pyridine in a flask provided with stirring and an ascending cooler surmounted by a Cl2Ca guard. Then 30 g of pig pancreas lipase (EC 3.1.1.3-SIGMA:
L3126) as well as 150 mmol of triglyceride or of the trifluoroethanolic ester. Stirring and heating are maintained at approximately 450C for approximately 39 hours. The progress of the reaction is followed by thin layer chromatography (plate of Merck-5719 silica gel, eluent: methanol 10-dichloromethane 90, developer: iodine).

 The crude mixture is then preferably extracted using a quaternary mixture consisting of water, acetonitrile, heptane and ethyl acetate.

 After several washes and evaporation of the organic phase, the expected pure product is obtained.

 If desired, the purification can be continued by recrystallization or by any other purification method. The yield of monoesters in position 6 of the methyl glucopyranoside is generally between 50 and 75% by weight.

According to this general process, the following methyl 6-O-alkanoyl-α-glucopyranosides were prepared:
EXAMPLE 1: 6-O-hevtanoyl-aD-ìucoyyrnnosîde of methyl
- white non-crystalline paste (Yield: 71%)
[alD20 +960 (C = 0.024; dichloromethane) - Elemental analysis: C14H2607; M 306.3
C% H%
Calc. 54.89 8.55
Tr. 54.45 8.37
The 13C NMR conforms to the expected structure.

EXAMPLE 2: 6-0-octanoyl- α -D-methyl glucopyranoside
- F = 45 C in the form of white powder (Yield: 60%)
- [a120 = + 92 (C = 0.023; dichloromethane)
- Elementary analysis: C15H18O7; M = 320.3
C% H%
Calc. 56.23 8.81
Tr. 56.13 8.71
The 13C NMR conforms to the expected structure.

EXAMPLE 3: 6-0-nonanoyl- α -D-methyl glucopyranoside
- F = 55 C in the form of a crystalline white powder (Yield 75%)
- [a] D20 = + 88.6 (C = 0.025; dichloromethane)
- Elementary analysis: C16H30O7; M = 334.4
C% H%
Calc. 57.47 9.04
Tr. 57.44 8.99
The 13C NMR conforms to the expected structure.

EXAMPLE 4: 6-0-decanoyl- α -D-methyl glucopyranoside
- F = 58 C in the form of a crystalline white powder (Yield 70%)
- [iD20 = + 86.1 (C = 0.024; dichloromethane)
- Elementary analysis: C17H32O7; M = 348.4
C% H%
Calc. 58.6 9.26
Tr. 58.72 9.17
The 13C NMR conforms to the expected structure.

EXAMPLE 5: 6-0-dodecanoyl- α -D-methyl glucopyranoside
- F = 700C in the form of a white crystalline powder (Yield 60%)
- [a] D20 = + 76.3 (C = 0.024; dichloromethane)
- Elementary analysis: C19H3607; M 376.4
C% H%
Calc. 60.61 9.64
Tr. 60.89 9.60
The 13C NMR conforms to the expected structure.

EXAMPLE 6: 6-0-hexadecanoyl- α -D-methyl glucopyranoside
- F = 870C in the form of a crystalline white powder (Yield 60%)
- [a] D20 = +67.80 (C = 0.024; dichloromethane) - Elemental analysis: C23H4407; M = 432.6
C% H%
Calc. 63.86 10.25
Tr. 63.75 10.10
The 13C NMR conforms to the expected structure.

 The compounds of Examples 2 and 5 were prepared according to the method using the triglycerides of octanoic and dodecanol acids respectively.

 The compounds of the other examples were prepared according to the method using a trifluoroethanolic ester of the corresponding acid.

Claims (10)

 1. Process for the enzymatic preparation of monoesters in position 6 of methyl glucopyranoside having the following general formula:

 in which: R represents an allyl radical, linear or branched, or alkenyl having from 6 to 21 carbon atoms or R represents a defined mixture of such allyl or alkenyl radicals, characterized in that it consists in reacting on a-D -methyl glucopyranoside, i.e. a fatty acid triglyceride of formula:

 or a tnfluoroethanolic fatty acid ester of formula:

 in which the radical R has the same meaning as above, the reaction being carried out in the presence of a lipase.  2. Method according to claim 1, characterized in that the reaction is carried out in an organic solvent medium.  3. Method according to claim 2, characterized in that the organic solvent is pyridine.  4. Method according to any one of the preceding claims, characterized in that the reaction temperature is between 35 and 500C and that the reaction time is between 20 and 50 hours.  5. Method according to any one of the preceding claims, characterized in that the proportion in moles of fatty acid triglyceride relative to the methyl glucopyranoside is between 5 and 0.5.  6. Method according to any one of the preceding claims, characterized in that the proportion in moles of the fatty acid trifluoroethanolic ester relative to the methyl glucopyranoside is between 5 and 0.5.  7. Method according to any one of the preceding claims, characterized in that the weight ratio of the lipase relative to the methyl glucopyranoside is approximately 3.  8. Method according to any one of the preceding claims, characterized in that the triglyceride is chosen from the triglycerides of heptanoic, octanoic, nonanoic, decanolic, dodecanoic and hexadecanoic acids.  9. Method according to any one of claims 1 to 7, characterized in that the tritluoroethanol ester is chosen from trifluoroethanol esters of heptanoic, octanoic, nonanoic, decanoic, dodecanoic and hexadecanol acid.  10. Monoesters in position 6 of methyl glucopyranoside as obtained by the process according to claims 1 to 9 and chosen from the group consisting of:  6-0-methyl heptanoyl-a-D-glucopyranoside,  6-0-methyl octanoyl-a-D-glucopyranoside,  Methyl 6-0-nonanoyl-a-D-glucopyranoside,  6-0-methyl decanoyl-a-D-glucopyranoside,  Methyl 6-0-dodecanoyl-a-D-glucopyranoside, and  6-0-methyl hexadecanoyl-a-D-glucopyranoside.