Preparation method of full benzyl-protected beta-alkylglucoside

Abstract

The invention discloses a preparation method of full benzyl-protected beta-alkylglucoside. The method is characterized by comprising the following steps of: mixing propineglucoside of full benzyl and a solvent in the ratio of 1mol:(10-100)L while stirring; adding an alcohol receptor while stirring; undergoing a glycosylation reaction in an FeCl3 / C solid acid catalyst at the temperature of 20-100 DEG C; after the reaction, filtering the catalyst out; and concentrating and purifying a filtrate to obtain a product, i.e., full benzyl-protected beta-alkylglucoside, wherein the receptor is an alcohol selected from phenylcarbinol, methanol, propenol, n-butyl alcohol and the like; and the equivalent proportion of the receptor to propyne alcoholic glycoside is (1.0-5.0):1. Compared with the prior art, the preparation method has the advantages of simple process, convenience for operating, low cost, high yield, avoidance of the use of high-toxicity chemical raw materials and environmental friendliness, and is a synthetic method of full benzyl-protected beta-alkylglucoside which has a wider substrate application range and is environmentally-friendly, economical and efficient.

Description

technical field [0001] The invention relates to the technical field of synthesis of pharmaceutical intermediates, in particular to a method for preparing all benzyl protected β-alcohol glycosides. Background technique [0002] At present, the preparation methods of β-alcohol glycosides are mainly divided into two categories: the first category is to use the adjacent group participation effect of the C(2)-position acyl group, and the second category is to use the C(2)-position ether protection to form a lock The intermediate living on the α face, the receptor attacks from the β face to get β-glucoside. The first type, due to the protection of the C(2)-position acyl group, greatly reduces the reactivity of the donor, the general reaction time is longer, and is accompanied by the competitive reaction of the orthoester by-product (Crich, D., et al, J. Org. Chem. 1999, 64, 5224–5229), if the reaction is carried out under basic conditions, the C(2)-position acyl protecting group ...

AI Technical Summary

Problems solved by technology

The first type, due to the protection of the C(2)-position acyl group, greatly reduces the reactivity of the donor, the general reaction time is longer, and is accompanied by the competition reaction of the orthoester by-product (Crich, D., et al, J. Org. Chem.1999, 64, 5224–5229), if the reaction is carried out under basic conditions, the C(2)-position acyl protecting group will also migrate to the C(1)-position ( Ensley, H. E. , et al, Tetrahedron Lett.2003, 4, 9363–9366)

The second type uses C(2)-position ether protection, which greatly improves the reactivity of the donor. For example, the C(2) position is an ether protection group (Boons, G. J. , et al, Angew. Chem. Int . Ed.2005, 44, 947–949) and the C(2) position is a picolyl protecting group (Demchenko, A. V. , et al, Angew. Chem., Int. Ed.2005, 44, 7123–7126), firstly, the donor used by the author is glucosinolate, which is highly toxic. The catalyst used in the above reaction is a heavy metal salt of trifluoromethanesulfonic acid, which is expensive and toxic. Finally, C( 2) The removal of the pyridylmethyl protecting group at the -position increases the reaction steps

There is also the complexation of trichloroacetimide esters with palladium-containing complexes (Nguyen, H. M. , et al, J. Org. Chem.2009, 74, 1650–1657), The catalyst is a metal palladium complex, which is expensive and toxic, and the obtained product also contains a certain proportion of α-glucoside

[0003] In summary, the β-alcohol glycoside products produced by the prior art have relatively high donor toxicity or poor stability, and the catalyst is expensive and toxic , the yield is low and there are by-products of α configuration, and the operation steps are cumbersome, which seriously restricts the wide application of β-alcohol glycoside products