The method of obtaining5-cyclo-24r-methyl - a-cholesterol-7,22-dien - 6-ola

 

(57) Abstract:

Usage: as an intermediate product in the synthesis of the phytohormone epibrassinolide. Essence: the product 3,5-cyclo-24-methyl-5-cholesterol-7,22-Dien-6-ol. The output 94% so pl. 95-96C. the Method speeds up the process, eliminates the need for purification of the target product. Reagent: 1: ergosterol. Reagent 2: methansulfonate. Reaction conditions: in the midst of pyridine, followed by treatment with sodium bicarbonate in aqueous acetone.

The invention relates to methods for the preparation of 3 , 5-cyclo-24 methyl-5-cholesta-7,22-Dien-6-ol of the formula (I), which is

an intermediate product in the synthesis of natural phytohormone of epibrassinolide with high growth promoting activity (1-3).

Known (4) the only method of obtaining 3-5-cyclo-24R-methyl - 5-cholesta, 7,22-Dien-6-ol (I) (prototype), which is that natural Sterol ergosterol (II) make toilet (III) the action of n-toluensulfonate in pyridine at room temperature during the day. Then toilet ergosterol (III) is subjected to the i-steroid rearrangement of 3-5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I) boiling in aqueous acetone in the presence of potassium bicarbonate for 5 minutes Total output Ciclopi is ergosterin (II), the need for treatment at both stages from the admixture of the compound (IV), and the duration of the process.

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The purpose of the invention is the increase of output 3 , 5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I) of ergosterol (II) and the reduction in the duration of the process.

This goal is achieved by the described method, which consists in the fact that ergosterol (II) processing methanesulfonamido in pyridine turn in mesilate (V), which by boiling in aqueous acetone in the presence of potassium bicarbonate programmirovaniya 3-5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I).

The method differs from the nearest known fact that in the i-steroid rearrangement instead tosilata ergosterol (III) is used mesilate (V).

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Known use for the i-steroid rearrangement nelfinavir 22-dehydrocholesterol (VI), containing in the loop. In only one double bond [5]. The output of the ketone (IX) in this case amounted to 79%.

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The use of nelfinavir instead tosilata does not in this case any benefits. Thus, the compound (XIII) obtained according to a similar pattern through the stage tosilata (XI) with yields of 80% (6). The application of the mesylates of sterols containing diene system in the cycle, q is retene is an example.

P R I m e R 1. Ergosterol (5 g, 1,210-2mol) is dissolved in 40 ml of pyridine and with continuous stirring, add 2,03 g (1,7710-2mol) methanesulfonamide. The reaction mixture was incubated for 15-20 min, then diluted with water and extracted with ether. The extract is washed with 20% acetic acid, then with water and saturated sodium bicarbonate solution. Dried over sodium sulfate, evaporated. Selected 5,88 g of compound IV. The yield of 98.2% So pl. 95-96aboutC. the infrared spectrum, cm-1; 1180, 1325 (O=S=D).

Range PMR (200 MHz , M. D.) to 0.62 (3H, 18-Me), of 0.82 (3H, I GC, 26/27 IU), 0,84 D. (3H, I GC, 26/27-IU) to 0.92 (3H, I GC, 24-IU), 0,96 C.

To a solution of 5.2 g nelfinavir IV in 700 ml of acetone is added a solution of 12 g of potassium bicarbonate in 100 ml of water. The reaction mixture is refluxed for 1-1,5 hours and Then evaporated about 1/3. diluted with 300 ml of water and extracted with ether. The extract is dried over sodium sulfate, evaporated. Selected 4,18 g Ciclosport I. the Yield of 96.2%. So pl. 131-133aboutC.

The infrared spectrum, cm-1: 3400 (OH).

Range PMR (200 MHz , M. D.); of 0.64 (3H, 18-Me) 0,826 d 3H, I GC, 26/27 IU), 0,846 D. (3H, I GC, 26/27 IU) to 0.92 (3H, 7.2 Hz, 24-IU) of 1.03 (3H, Hz, 21-Me), a 1.08 (3H, 19-Me) 3,42 DD (1H, I14.5 GHz, I21.2 Hz, C6-N, 5.2 m (2N, C22-H and C23N); 5,47 m (1) - Rev. and allows to increase the yield of the target compounds from 49 to 94%, to reduce the length of the process, and eliminates the need for purification of the target product.

METHOD for the preparation of 3, 5-CYCLO-24R-METHYL - 5-CHOLESTEROL-7,22-DIEN - 6-OL, including the interaction of ergosterol with sulphonylchloride in pyridine and boiling received alfaprostol in aqueous acetone in the presence of potassium bicarbonate, characterized in that, to reduce processing time and increase the yield of the target product, as sulphonylchloride use methansulfonate.

 

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SUBSTANCE: invention represents new derivatives of 17,20-dihydrofusidic acid of the formula (Ia)

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EFFECT: valuable medicinal properties of compounds.

22 cl, 7 tbl, 41 ex

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EFFECT: improved preparing method.

2 cl, 3 ex

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EFFECT: improved producing method.

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SUBSTANCE: polyaminosteroid branched derivatives of general formula I are described, where R1 is saturated or unsaturated C2-C10alkyl (conjugated or branched) or methyl, R2 is COOH or branched polyamine fragments, R3 is H, OR19, where R19 is H or C1-6acyl, R4 is H, R5 is H, CH3, R6 is H, CH3, R7=R8=R9=H, R10 is H, CH3, R11 is OH,-OSO3, - O-acyl, -(Z)n-(NR-Z)p-N(R)2, Z is linear hydrocarbon diradical, n=0, 1, p=1, R-H, C1-6alkyl, C1-6aminoalkyl, possibly substituted by C1-6alkyl, R12=R13=R15=H, R16 is H, OH, R17 is H, R18 is H, CH3, possible double bond. Compounds possess bactericidal activity and can be used for prevention of bacterial infections.

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27 cl, 31 ex, 1 tbl, 2 dwg

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19 cl, 38 ex, 12 tbl

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