SU787414A1 - Method of preparing 1,2-di-o-palmitoyl-3-o-/6-o(1,2-di-o-palmitoyl-stannum-glycero-3-o-phosphoryl)-alpha-d-glucopyranosyl/-stannum-glycerine - Google Patents

Description

The invention relates to chemical compounds of natural compounds, namely to the chemical method of obtaining 1,2-au-O-palHjidijo e about dHt Hz, s1.90o - dn L

belonging to the class of biologically active compounds - phosphoglycolipids - substances that play the role of lipid core to attach to the hydrophobic bacterial membrane hydrophilic lipoteichoic acid, which has immunological properties of p. 1.

Study of the metabolism of phosphoglycolipia and its contribution to the functioning

cell membrane apparatus on model artificial membranes cannot be satisfied with inaccessible natural samples representing sobs complex mixtures of compounds with different JJJ set of hydrophobic components. The need for phosphoglyksipid molecular samples brings to the fore the problem of the directed chemical synthesis of this new class of compounditoyl-3-O- (1,2-di-O-palmito-yl- $ P-glycero-3-O-phosphoryl) - ot- T) -glucopyranosyl - $ YT-glycerol of the general formula I but it-ociodjsHsi 3izdodocii5H3i

SRI. New data on the structure of biological, membranes of pathogenic bacteria in the TC with an additional contribution to the fight against infectious diseases.

A known method for producing phosphoglycolipiaa by isolation from bacteria

Pseudowonas d-im-ivivita- 2.

The method is characterized by considerable experimental difficulties due to the duration of the process and the negligible yield of the target product (0.9%). In addition, the phosphoglycolipid obtained during isolation from natural sources is not an individual chemical compound, but a homologous mixture in the fatty acid structure of individual phosphoglycolipids. The absence of individual compounds in biochemical studies makes their interpretation difficult.

The invention is the development of a new method for the chemical synthesis of the individual phosphoglycolipid 1,2-di-O-palmitoyl-3-O-b-O- (1,2-ai-O-palmitoyl-α-glycero-3-O-phosphoryl) D- glucopyranosl) -5U1-glycerin, which provides a significant increase in the yield of the target product.

The goal is achieved by the method which consists in the fact that 3,4,6-tri-O-acetyl-R-1) -glucopyranyl chlorides (G1) are reacted with 1,2-di-O-benzyl-511 glycerol ( Ш) in dry dioxane in the presence of 2-valence mercury succinate as a catalyst and stoichiometric amounts of sodium iodine. Adding sodium iodide to the reaction mass accelerates the reaction and increases the yield of 1,2-di-O-6enzyl-3-O- (3, 4,6-tri-O-acetyl-D-glucopyranosyl) BztOClHz

-5I-1 licerin (IV) due to the formation of a more reactive intermediate glucosyl iodide. The compound (IV) obtained with a 67% yield according to gas-liquid chromatography, consists of 93% of the required amount of about 6.66.

Next, the compound (IV), by the action of a 3-fold excess of acetic anhydride in dry pyridine, is converted into 1,2-di-O-β-benzyl-3-0- (2, .3,4, b-tora-O -acetyl-.D-glucopyranosyl) -5n-glycerol (V), followed by removal of the benzylkyl protection by hydrogenation to palladium black in ethyl acetate. The obtained 3-0- (2,3, 4,6-tetra-O-acetyl-T) -glucopyranosyl) -6U-glycerin (VI) is acylated: with a 3-fold excess of palmitic acid chloride in the medium of boiling toluene in the presence of dry pyridine and 1,2-di-O-palmytoyl-3-O- (2,3,4,6-tetra-O-acetyl-D-glucopyranoyl) -51t-1 lysterin (UI), which are formed in this way, are separated for anomers by column chromatography on silica gel U 1OO / 160.cL-Anome of compound (UN) by boiling with hydrazine hydrate in methanol, transferred to 1,2-di-O-palmitoyl-3-O- (oC-D- glucopyranosyl) -5) 1-glycerin (Y111).

Phosphorylation of the compound (UP1), taking into account the increased reactivity of the primary hydroxyl group as compared to the secondary, is carried out by reacting the latter with 1,2-di-0-papmitoyl-5) 1-Glycero-3-0-4) osphoric acid in the presence of 2,4-6-triisopropylbenzenesulfonyl in pyridine with a ratio of 2: 1: 3. The desired product is isolated by known techniques. The process is carried out as follows.

HodHz -o

OYHo -f

but H-c -orioeisH3i

Hjcioeoeigiiaj

UTTG ai-isOdo Hz 31Ч50С10 -dH о Нгс1о Р 1ос1 but j- Example 1. A mixture of 0.83 g of 3,4,6-tri-O-acetyl- | b - D-glucopyranosylchloride (11) and 0.38 g of calcined sodium iodide in 6 ml of dry dioxane is stirred for 30 minutes at 19-20 ° C, 1.35 g of 1,2-di-O-benzyl-5i-glycerol (P) and 0.415 g of 2-to-valence mercury are added and stirred for another 20 hours. The reaction mass is filtered, evaporated. The residue is dissolved in 1OO ml of ether, washed with solution No 3-10 ml), water, dried, evaporated in vacuo. The resulting oil was dissolved in 3.6 ml of dry pyridine and 3 ml of acetic anhydride was added. Leave for 16 hours at 19-20 ° C. Add 5 ml of water, allow to stand for 1 hour and evaporate in vacuo. The residue is dissolved in 50 ml of chloroform, washed with cold water (3 × 10 ml), saturated T4 O (3 × 5 ml), water, and dried. The substance was isolated by column chromatography on silica gel L 4 O / 100, eluor chloroform. The output of 0.86 g (67%) ,,, BS (with 1.1, SNS1), Tr. 0.5 Found,%: C 61.63; H 6.30. C-VI Calculated: C 61.78; H 6.31. Then, 0.27 g of 1,2-di-O-benzyl-3-O- (2,3,4,6-tetra-O-acetyl-D-glucopyr. Nosyl) -8i-glycerin (U) is hydrogenated to palladium black in 8 ml of dry ethyl acetate at 20 ° C for 3 h. The catalyst is filtered off and the filtrate is evaporated in vacuo. Vykod 3-0- (2,3,4,6.-Jgtepa-0-Atsetsl-TZ-glucopyranosyl) - Zp-glycerin (Y1) 0.2 g (96%), Na +100.4 (s 1, 0, sns ,,, 4. Found,%: C, 47.20; H, 6.08. Sb ia5i3jcli50ciodHz Hjidisodo

Claims (1)

KZ e 0 - P- (OH) 2 IX Con HoY n-c1-odoeigJiai HzdociodigHii Calculated,%: C 47.39; H 6.16. Following this, to a solution of 0.2 g of the obtained compound (U1) in 15 ml of dry toluene and 1.5 ml of dry pyridine at 0 ° C and vigorous stirring is added dropwise 0.7 g of palmitic acid chloride. After 3 h, the reaction mass is brought to a boil and boiled for 4 h, then filtered, the precipitate is washed with toluene, and the filtrate is evaporated. The substance was isolated by column chromatography on silica gel, 10O / 160, eluting with pegrol ether / 75:25. oL-1,2-di-O-Palmitoyl-3-O (2,3,4,6-tetra-O-acetyl-TE-glucopyranoyl) -Sn-glycerol (UE) number: yield O, 34 g (80 %), t. PL7 29-30 ° С,, l (c 1.1, CNSS),, 6. Found,%: C 65.37; H 9.58. - 49 5b 14 Calculated,%: C 6 5.5 O; H 9.65. j Anomer of Compound (UE): yield: 0.026 g (6%), so pl. 79-80 SMO-1 -6.9 (with O, 5, CHCCj) ,, 57. 0.5 g (i-anomer of compound (UE) is boiled in 26 ml of methanol containing 0.22 ml of hydrazine hydrate, 1.5 h. The reaction mass is cooled, neutralized with formic acid, maintained at 24 h. Sediment filtered off, recrystallized from methanol. The yield of 1,2n1I-O-Palmitoyl-3-0- (oL Elucopyranosyl) -8i-glycerol () 0.2 g (52%), mp. 8182 Col: I +37 (c 0.5, CNSS.), 8. Found:%: C 66.83; H 10.21. Calculated,%: C 67.08; H 1 O, 75. Then 70 mg of the compound (VHS) and 43.5 mg of TPN are dissolved in 3 ml of dry pyridine freshly distilled over sodium and stirred at 19–20 ° C; 40 minutes. Then add 31 Mg 1,2-di-0-palmygoyl-511-glycero-3-O-phosphoric acid (GC) and continue stirring for 2-3 days. 3 m of water are poured in and after 30 minutes the solvent is distilled off, the residue is chromatographed on a column of silica gel L 10-160, eluting the substance with a mixture of chloroform-methanol, 97: 3. The yield of the target product (1) 45 mg (30%), calculated on the compound (At so pl. 53-53,5 ° C, about (( C 1.0, CCHE), Tg 0.39, Found: C, 66.72; H 1O, 29; P 2.13. 16% P H3jei50CioeH2 Hjjciisodo EN characterized in that, in order to increase the yield of the target product, 1,2-di-0-benzyl-5I-glycerol glycosylate 3,4,6-tri-O-acepsh1-) -D - glucopyranoyl chloride of the general formula LSOSN, C OH in dry dioxane in the presence of T9 2-valent mercury and a stoichiometric amount of sodium iodide, the resulting compound is treated with a 3-fold excess of acetic anhydride in dry pyridine, followed by 1,2-di 0-benzyl-3-0- (2,3, 4,6-tetra-O-acetyl-T) -glucopyranosyl) 9k -glycerin is hydrogenated to palladium black in ethyl acetate Isolated product is acylated with a 3-fold molar excess of palmitic acid chloride in toluene in the presence of dry pyridine Calculated%: C, 67.07; H 10.66; R 2.28. The total yield of the desired product on the starting compound (I) is 8%. Thus, the chemical synthesis of 1,2-di-O-palmitoyl-3-0-Gb-0- (1,2-di-0-palmitoyl-Z-glycero-3-0-phosphoryl) -c {. - D -glucopyranosyl -Sh-g-lycerol (1), as a result of which the yield of the target product increased 8.9 times. The invention of the method for producing 1,2-di-O-palmitoyl-3-0-b-O- (1,2-di-O-palmitoyl-5l-glycero-3-O-phosphoryl) -o (.- E- GlucopyranosylZ-Zi-glycerin of the general formula Oeng He-odod-tsHji HzCJociOCJisHji at boiling, anomeric mixture of 1,2-ai0-palmitoyl-3-0- {2,3,4,6-tetra-O-acetyl-T) -glucopyranosyl ) The 5 grams of 1-idrins are separated into anomers by column chromatography on silica gel L 10 O / 160 and the c-anomer is boiled with hydrazine hydrate in methanol and converted into 1.2-di-0-palmitos 1-3-O (c (- 1) -glucopyranosyl) -5 -glycerin, which is reacted with 1,2-ai-O-palmitoyl-BI-lycero-3-O-phosphorus acid in the presence of 2,4,6-triizopropilbenzolsulfohlorida in pyridine at a component ratio of 2: 1: 3. Sources of information taken into account in the examination of i SViaw N. BacieridE g-e cotipids qna, ophosp1io ", - ipid .. AAjo-otiioe., -1915, V./12 ,;). 141 .. a.i l iwBon S.G-aind Bete M-E-Tlne pbosp og tucotipid from Pseudomonae divninuia.-. et biopti S .. 1) 1l, N.248, pp.293-299 Sprottrm