SU1293167A1 - Method of producing cis-1-0-(1-alkenyl)-glycerin - Google Patents

Abstract

The invention relates to glycerol derivatives, in particular cis-1-0- (1-alkenyl) -glycerols (GL), which are used for the synthesis of aldehydrogenic phospholipids of natural structure. Simplification of the process is achieved by using a strongly basic anion exchange resin in T -form and another mixture of solvents. Synthesis of GL compounds is carried out by adding to equivalent amounts of fatty aldehyde and glycero-2,3-cyclocarbonate in a chloroform-ether-dimethylformamide solvent mixture with a ratio of components, 2: 1: 1, of a strongly basic anion exchanger in J-form at 25- 30 ° C, then with intensive stirring, a 2.0-2.5 fold excess of triethyl amine is added dropwise. After 4.5-5.0 hours, the anion exchanger and the precipitated precipitate are separated and the reaction mass is subjected to chromatographic separation and the isolated compound is recrystallized. The output of GL 38-40%. The method provides a simplified process by reducing the steps, reducing the process time 2.5 times, reducing the consumption of the initial reagent. g (L

Description

The invention relates to an improved process for the preparation of glycerol derivatives, namely cis-1-0- (1-alkenyl) -glycerols, which are used as starting compounds for the synthesis of aldehydogenic phospholipids of natural structure belonging to the class of biologically active compounds.

The purpose of the invention is to simplify the process by reacting glycero-2,3-cyclocarbonate with fatty aldehyde in equivalent amounts in a chloroform-ether-dimethylformamide solvent mixture at 25-30 ° C in the presence of a strongly basic anion exchanger in the Jj form and 2.0 2.5-fold excess triethylamine.

Example 1. Synthesis of CIS-1-0- - (1-hexadecenyl) -Gas-glycerol.

Amberlist A-26 in the J-form during a day is suspended in the ether solution of iodine. The resin is separated, washed with ether to remove excess iodine and dried in an oil pump vacuum (resin capacity according to J-aHHOHy is determined by iodometry - 3.2 mg eq / g) about 3 mmol hexadecanol and 3 mmol gus-glycero-2,3 -cyclocarbonate was dissolved in 120 ml of chloroform-β-ether-dimethylformamide (DMF) 2: 1: 1 solution, heated to 25-30 ° C, 1 g of Amberlist resin A-26 was added in J-form and dropwise 0.285 ml of triethyl amine (2-fold excess) was added with vigorous stirring. After 5 hours, the resins and the precipitate precipitated are separated and washed with 2x50 ml chloroform. The combined mother liquor is evaporated, and the mixture is cis-. -trans-isomers 1-0- (1-hexadecyl) -ras-glycerol were isolated by silica gel column chromatography on an ether-n solvent gradient. 1: 1 ether – p ether, 9: 1 ether. Separation of the cis-trans isomers is carried out by reverse phase chromatography on TMS silica gel in a 98: 2 methanol-water solvent gradient: methanol-water-ethanol 92: 1 : 7, The products are recrystallized from ether. The total yield of the mixture of isomers 0,491 g (51%),

Cys-1-0- (1-hexadecenyl) -as-glycerol. Yield 0.339 g (48%); Rf 0.48 (ether-PoEther 9: 1, silufol); melting point 35,

IR, cm: 3550, 3000, 1675, 1425, 1380 „.

 H-NMR, o, md: 0.88 (t, CH); 1.26 (s. CH); 2.12 (d, OH); 3.85 (m.); 4.47 (m, JSN, J 6.1 Hz 5.95 (d, o CH, J 11.9 Hz),

Found,%: C 72.48; H 12.34.

Calculated:%: C, 72.56; H 12.18, Trans-1-O-C1-hexadecenyl) -gas-glycerol. Yield 0.132 g (13%); R, 0.48 (ether-p, ether 9: 1, silufol); melting point 36.1 ° C,

IR, 1, cm: 3550, 3000, 1645-1655, 1425, 1380, n-NMR, & , m, d,: 0.8 (t ,, SND); 1.26 (s. CH); 2.12 (d, OH); 3.85 (m, CH 0); 4.75 (m, PCH ,, J 6.1 Hz); 6.26 (d ,, p. CH, J 11.9 Hz),

Found,%: C 72.51; H 12.26,

S.dNzOz

Calculated,%: C, 72.56; H 12.18,

Example 2, the synthesis of CIS-1-0- - (1-octadecenyl) -Gas-glycerol,

Amberlist A-26 in the J-form is suited for 24 hours in ethereal iodine. The resin is separated, washed with ether to remove excess iodine and dried in an oil pump vacuum (the resin capacity was determined by iodometry using a J-anion — 3.2 mg eq / g), 3 mmol octadecanol and 3 mmol gas-glycero-2, The 3-cyclocarbonate is dissolved in 120 ml of a 2: 1: 1 chloroform-ether-DMF solution. heat to 25-30 ° C, add 1 g of Amberlist resin A-26 in the J form, and add 0.360 ml of triethylamine (2.5-fold excess) dropwise with vigorous stirring. After 4.5 hours, the resin and the precipitate precipitated are separated and washed with 2x50 ml of chloroform. The combined mother liquor is evaporated, and the mixture of cis-trans isomers of 1-O- (1-octadecenyl) -glycerin is separated by silica gel column chromatography in a solvent gradient of ether-β, ether 1: 1 - ether-p, ether 9: 1, Separation into cis and trans isomers is carried out by reverse phase chromatography on TMS silica gel in a solvent gradient of methanol-water of 98: 2 to methanol-water-ethanol 92: 1: 7 The products are recrystallized from ether. The total yield of the compound is 0.534 (53%) o

Cys-1-O- (1-octadecenyl) -as-glycerol. Yield 0.401 g (40%); R | 0.48 (ether-n, ether 9: 1, silufol); melting point 38

12931

PC, cm-: 3550, 3000, 1675, U25, 13.80,

 I-NMR, 5, MD: 0.88 (t., CH p; 1.26 (s., CH); 2.12 (d., OH); 3.85. (M,) ; 4.47 (m., P-CH, J 6.1 Hz); 5 5.95 (d., CH B, J 11.9 Hz) o

Found,%: C 73.49; H 12.44.

WITH,. H ,, Oh,

Calculated,%: C 73.63; 11 12.36.

Trans-1-O- (1-octadecenyl) -gas-gly-Oh cerium. Yield 0.133 g (13%); RjO, 48 (ether-PoEther 9: 1, silufol); melting point 39.8 ° C.

IR, f, cm: 3550, 3000, 1645 - 1655, 1425, 1380.15

 H-NMR, & M.D .: 0.88 (t, CH.); 1.26 (s. CH); 2.12 (d, OH); 3.85 (M.,); 4.75 (m, p-CH, J 6.1 Hz); 6.26 (d „, oi-CH, jn, 9 Hz)

Found,%: C 73.47; H 12.42.

20

.Oz.

Calculated,%: C 73.63; H 12.36.

According to the proposed method of producing cis-1-O- (1-alkenyl) -glycerines, the technology is greatly simplified by carrying out the synthesis process in one stage, the process time is reduced by 2.5 times, the consumption of glycero-2,3-cyclocarbonate is reduced in 3 times, toxic agents such as acetyl chloride and phosphorus pentachloride are excluded. Way

Editor M. Dylyn Order 343/25

Compiled by N. Kapitanova

Tehred A. Kravchuk Proofreader O. Lugova

Circulation 372 Subscription VNIIPI USSR State Committee

for inventions and discoveries 113035, Moscow, Zh-35, Rauschska nab, 4/5

Production and printing site, Uzhgorod, st. Project, 4

674

also allows the regeneration and reuse of ion exchange resins.

Claims (1)

Invention Formula The method of obtaining CIS-1-0- {1-alkenyl) -glycerin of formula CHri-0-CH CH-R w-he (I) CH2-OH where R is alkyl, based on glycero-2,3-cyclocarbonate and fatty aldehyde, using triethylamine and chromatographic separation of isomers, characterized in that, in order to simplify the process, to equivalent amounts of fatty aldehyde and glycero-2,3-cyclocarbonate in the mixture chloroform: zfir: dimethylformamide (2: 1: 1) at 25-30 ° C, a strong base anion exchanger in J, 7-form is added and, with vigorous stirring, 2.0-2.5-fold excess of triethylamine is added, after 4.5- 5.0 hours the anion exchanger and the precipitate precipitated are separated, the reaction mass is subjected to chromatographic separation u- and the isolated cis-1-0- (1-alkenyl) -glycerin are recrystallized.