Cyclic cholane carboxylate derivative, preparation method and uses thereof

Abstract

The present invention provides a cyclic cholane carboxylate derivative and a preparation method thereof, and uses of the cyclic cholane carboxylate derivative in industrial preparation of 25-hydroxycholesterol (1), wherein R1 in the cyclic cholane carboxylate derivative represented by a formula I is straight chain or branched chain C1-C12 alkyl, R2 is methyl or ethyl, and the formula (I) is defined in the specification. According to the present invention, the starting raw material stigmasterol of the 25-hydroxycholesterol (1) synthesis process route has characteristics of low price, easy obtaining and reliable commercial source; and particularly during the constructing of the 17-position side chain of 25-hydroxycholesterol (1), the reaction conditions are mild, the reaction steps are simple, the special and dangerous reagents are not required, the harsh reaction conditions are not required, the redundant reaction steps are not required, the chromatographic separation and purification is not required, the industrial production is easily achieved, and the significant progress is achieved compared to the prior art.

Description

technical field [0001] The invention provides a class of cyclocholane carboxylate derivatives, a preparation method thereof, and an application thereof in the industrial preparation of 25-hydroxycholesterol (1). Background technique [0002] 25-Hydroxycholesterol (1) is a key intermediate for the preparation of many important vitamin D derivatives. The vitamin D derivatives include but not limited to idecalcitol (2), calcitriol (3) and calcifediol (4). [0003] Eldecalcitol, chemical name (5Z,7E)-9,10-broken cholesterol-5,7,10(19)-triene-1α,3β,25-triol, other name ED-71, the chemical structural formula is shown in formula 2. Idecalcitol is a vitamin D drug, clinically used for the treatment of osteoporosis. [0004] [0005] Calcitriol, chemical name (5Z,7E)-9,10-broken cholesterol-5,7,10(19)-triene-1α,3β,25-triol, other name 1α ,25-Dihydroxyvitamin D 3 , the chemical structural formula is shown in formula 3. Calcitriol as Vitamin D 3 The active metabolite is clini...

AI Technical Summary

Problems solved by technology

[0014] In route two, although the starting materials are cheap and easy to obtain, there are relatively large deficiencies in the construction of the 17-position side chain of 25-hydroxycholesterol (1): first, tetrahydropyranyl (THP)-protected 3-methyl Base-1-butyn-3-alcohol (13) requires additional preparation; Second, the coupling reaction uses a special dangerous reagent n-butyllithium; moreover, the resulting coupling product (14) still needs to pass through 10% palladium carbon Catalytic hydrogenation, acidic hydrolysis deprotection to obtain 25-hydroxycholesterol (1)

[0020] The defect of route four is that the source of starting material 24-dehydrocholesterol derivative (former II) is unclear

In addition, in the invention patent CN104130306B, the chemical structural formulas of Proto I and Proto II do not indicate the stereo configuration of the chiral carbon

[0021] In summary, 25-hydroxycholesterol (1) is a key intermediate for the preparation of various important vitamin D derivatives, but there are obvious defects in the existing methods for the preparation of various 25-hydroxycholesterol (1)

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