SU691445A1 - 2-methyl-2-(3-carboxypropyl)-3-(1,4,5-trimethyl-2,3-epoxyhexyl)-cyclopentanol-1 as an intermediate compound for syntesis of prostaglandines or their analogs and method of its preparations - Google Patents

Description

An unstable aldehyde II is formed in aqueous TPB-butanol - the starting material in the synthesis of prostaglandins and their analogues. Blow out the connection. II from starting compound III is about 2%. Y (R (i02H) VI ((iHj) OH he yiir Compound. II is formed as a mixture of two isomers at the C -atom (which is indicated by a wavy line), in fact, this method is not sterile selective. The other disadvantages are significant the duration (about two weeks) of the oxidation process, the use of deficient and toxic substances (e.g., Oj o) and the need for chromatographic separation of low-resistant, reaction products ....; Compound l was: n; the result: conversion of 6-methoxy- Z-indiol in triphenyl-6-methoxy-Z-Indanyl by the reaction of the latter with the meter-b-forshe teptayoate in dimethyl oxide with the following isomerization (in the environment of tri-O-acetic acid), hydroxylation (Os pyridium, not) and reboot (Os, with paratoluene, headache, I am not able to go to the monitor), I go to the monitor, I use the program to adjust the concentration of the oxymethromide to the dimethylbromide with the help of the following test. The following reactions range: acetylation (in diethylenthlycol, in the presence of paratoluene thiol sulfo acid), washing with alkali in methanol, B; stabilizing (lithium in liquid ammonia) and hydrolysis (5%, acetic acid (lithium in liquid ammonia) and hydrolysis (5%, acetic acid (lithium in liquid ammonia) and hydrolysis) After the methyls of an (action, CHaJ and hexamethylphosphoramide in THF), the compound was reduced (the effect of ZiAftlOBu- in. THF on), deacetylated (the action of HclQ in THF), is isomerized (methylate sodium in methane) to ketone and restored by palladium. After chromatography of the pis of the stock thus obtained on silica gel, the 4glg-6-oxyl-7-and ethyl-2-oxo-3-hydrindangöptanoate methyl ester was extracted. Compound XII was obtained by meylation of the latter in pyridine and the subsequent {elimination reaction (in dimethyl sulfoxide at 7 h) bwio (complicated by chromatography on silica gel). By oxidation of compound XII (combined action of CMO. And NaJO.) Followed by pimerization (the action of Narti methylate in methanol) secoislot XIII was obtained, which was then converted to its benzyl ether and oxidized (the action of overtrifluoroacetic acid in methylene chloride in the presence of NaHPO) to compound XIV, and the necessary compound IX was obtained from it — the starting substance in the synthesis. —Simple-glandins (Sn YOUNG.R (a (CIS), (; O21,)) H (YNN iH Xj ,,,, v (CH ) j (02H {(JHzls JOzCKj) However, this method has a substantial; yod6stat and, firstly, the original connection is straightforward, since its synthesis is multistage (since 10th stage is dyed) and requires using of deficient reagents -, CFg CO, H, CH - jN Pd / C, and secondly, the transition from X and IX is multistage, and The stages require a thorough purification of the reaction products. All this significantly complicates the preparation of the compound IX and leads to a reduction in the output; an objective of the invention is the new cyclopentane ancestor of the prostaglandine and its analogs with the required synthesis of substituents and the required amounts of substituents with the required amount of the prostaglandine and their analogs with the required number of | development of a simple and convenient for practical implementation both synthesize the said compound based on accessible polycyclic compounds and non-crystalline chemical chains. In accordance with the new retention of the cyclopentane precursor, namely 2-methyl 2- (3-carboxypropyl) -3- (1,4,5-trimet: yl -2,3-epoxyhexyl) -cyclopentanol-1 has the structural formula I. The method of obtaining compound D consists in the fact that ergocalcium ferol (vitamin Djj) or photomolar is sequentially treated with a 2–5-fold weight excess of potassium permanganate in an inert solvent in an acidic phase and metachloroperbenzoic acid, followed by hydrolysis of the obtained

with this product. Hydrolysis is desirable to conduct in an alkaline environment.

H

L o

HE

l.RCOjR AND S YNZ 2NO-O

As an intermediate compound HHH, a derivative of r4g r-hydrindane series (given in square brackets) is formed, similar to compound 5C. Breaking a six-membered ring in it leads to the formation of compound I without stereochemistry. .

The oxidation is carried out at room temperature for 30-60 minutes while stirring a solution of ergocalciferol (in a solvent inert with respect to the oxidizing agent, preferably in benzene), first with an excess of potassium permanganate in an acidic medium, and then the resulting neutral product is subjected to a superacid. Subsequent hydrolysis allows to obtain the target product I with a yield of about 6%

As a starting material, it is possible to use both chemically h: erst ergocalciferol, and its intermediate product - photo moth (mixture / products of ergosterol photolysis) without a significant change in yield.

Note: 1. To a solution of 12 g of potassium hematanganate in 800 m of water with vigorous stirring, add a solution of 4.00 g of ergocalciferol in a .600 ml can and 100 ml of 7% waterborne sulfuric acid. The reaction mixture is stirred at room temperature for 45 minutes and then filtered. The filter cake was washed with ether (2.x X 100 ml), the ethereal solution was combined with the mother liquor. The organic layer is separated (prol) / sewed first with water (400 ml.), And then with 5% aqueous alkali solution (2 x 100 ml) and again with water until neutral. After drying over anhydrous sodium sulphate, the solvent is distilled off, 3.01 g of light yellow meson are obtained in the residue (neutral product A),

To product A, dissolved in 5 ml of methylene chloride, a solution of 2.0 g of methachlorobenzoic acid in 20 ml of methylene chloride is added and the mixture is stirred at room temperature for 40 minutes, then part of the solvent (about 1/2 volume) is distilled off and filtered. After treatment of the precipitate and the mother liquor, as described above (this uses reduced amounts of 10 times: ether, water and solution nj), 0.315 g of a light yellow oil is obtained (neutral product B) ..

35 ml of a 5% aqueous hydroxide solution is added to product B

5 potassium and the mixture is heated at 90 ° C .10 min. After cooling to room temperature, it is washed with ether (3 x X 30 ml) and then poured with hydrochloric acid and extracted with ether. This

0 ether extract; washed with water to a neutral medium and after drying, distillation from the solvent. In the residue, the following is obtained: a clear, viscous oil identified as 2-methyl-2- (3-carb5 oxyppropyl) -3- (1,4,5-trimethyl-2,3-epoxyhexyl) -cyclopentanl-, Output 6.1 % (from theoretical).

Molecular weight 326 - according to mass spectrometry data (calculated for 326),

PRI mme R 2. From 4.00 g of a photomicrograph by oxidation with potassium permanganate using the procedure described above (for Mer 1), 1.17 g of product A is obtained,

5 after oxidation of which, in a methylene chloride solution, 0.6 g of metachloroperbenzoic acid is obtained within 1 hour; oy, o, 176 g of product B. When the hydrolysis of the latter with 5% aqueous solution of c; 0.079 g is formed.

0 necessary predecessor (I), derived from ergocalciferol. Output 4, 0% (from theoretical).

From the above examples it is clear that

5 The proposed method for producing cyclopentane prostaglandin precursor with a certain stereochemistry of substituents has several advantages over the known ones.

0 ways. Synthesis does not require a lot of time and costs, simple to implement, involves the use of available raw materials and chemical reagents.

five

Claims (1)

Invention Formula 1, 2-Methyl-2- (3-carboxypropyl) -3- (1,4,5-trimethyl-2,3-epoxyhexyl) -cyclopentane ol-1 of the formula 0 t (iHj CHACH ,, .-- ..: -: - AsJ-.г ::: Ai t: rv: J iv-S; v;: ....- .. - ... g.-- -i ib iieii fc - A -; -.-. .--. -.-.-...-.- .. j -.-...-, -. ,, ..:, -, ..-. , - - ... ----- ---- 76914458 as intermediate for acid-inert solvent . the prostaglandins or their analogs. and metachlorophenol acid with POT2. The method of obtaining the compound by the subsequent hydrolysis obtained at p. 1.3 a k lu h a yu y and u with that this product. ergocalcis: erol or Photosmola after-3. The method according to claim 2, about tl and h, is encompassed by 2-5-fold in terms of the fact that the hydrolysis is carried out weight excess potassium permanganate alkaline medium.