Method for oriented synthesis of unsaturated conjugated alcohol

Abstract

The invention discloses a directional synthesizing method of unsaturated conjugated alcohol, which is reacted by unsaturated conjugated ketone and chirality reducer BINAL-H to generate S or R directional solid conjugated unsaturated hydroxy. The invention improves the solid selectivity and receiving rate of object product.

Description

Technical field: The invention relates to a method for directional synthesis of unsaturated conjugated alcohols. Background technique: The method for reducing the carbonyl group in the conjugated unsaturated ketone compound to an oriented hydroxyl group is very necessary in the preparation of some drugs. For example, in the modification of the side chain of vitamin D compounds: MC903 (calcipotriol, see formula III) or 1,24-(OH) 2 D. 3 (see formula IV). In the preparation of vitamin D analogs, specific stereochemistry of the C-24 hydroxyl group is necessary for full expression of biological activity. According to current methods, the stereochemistry required can be introduced by three methods: (1) Calverley, Tetrahedron 4609-4619, 1987 reported a diastereomeric mixture of C-24 hydroxyl epimers separated by chromatography; (2) ) US6262283 disclosed the stereoselective reduction of the corresponding C-24 ketone; (3) Calverley, Synlett 157-159, 1990 reported the attachment ...

AI Technical Summary

Problems solved by technology

Calverley uses NaBH 4 / CeCl 3 (Tetrahedron Vol43, No.20pp 4609to 4619, 1987) or AlLiH 4 As a reducing agent for the reduction reaction, the stereoselectivity is poor, and vitamin D 3 -22-en-24-one is 24-alcohol, the ratio of 24S and 24R configuration product is 38:61, because the target hydroxyl content is low, purification is difficult, separation effect is poor, and the cost of separation and preparation is high; M.Ishiguro etc. reported in J.C.S.Chem.Comm., 115-117, 1981, a method for stereoselectively reducing C-24 ketones to desired epimer C-24 alcohols, such as for the preparation of cholesterol derivatives; patent 2005087719 A method for the synthesis of calcipotriol with boron-containing derivatives as reducing agents in the presence of chiral auxiliary agents has been reported. The method has good selectivity, and the ratio of 24S and 24R configurations in the product is not less than 56: 44, but the reduced substance needs to use SO before participating in the reduction reaction 2 For protection, deprotection is required after the reduction reaction, and there are many procedures

Images