Stereoselective total synthesis method of (+)-biotin

Abstract

The invention belongs to the organic chemistry technical field, in particular to a (+) - biotin stereo-selective full synthesis method. The synthesis method comprises the following steps of preparing meso cyclic anhydride via ring-closing reaction and acyl halide dehydration with diacid as initial materials; preparing (4S, 5R)-half ester under the presence of cinchona alkaloid via enantioselective ring opening; then producing intermediate product (3aS,6aR)-lactone, (3aS,6aR)-thiolactone, (3aS,4S,6aR)-double-benzyl biotin and the derivative of the same via selective reduction, acid promoted cyclization, Fukuyama and coupling reaction and so on; debenzylating and ring opening upon the function of inorganic acid, and producing (+)- biotin via cycization reaction in inorganic base solution upon catalysis of activated carbon. With the synthesis method, raw materials are readily available, reaction conditions are mild and operation is easy; the catalyst used has good stability, is easy to be recycled and is suitable for industrial production.

Description

Stereoselective Total Synthesis of (+)-Biotin technical field The invention belongs to the technical field of organic chemistry, and in particular relates to a stereoselective total synthesis method of natural product (+)-biotin. Background technique (+)-biotin ((+)-biotin) I, also known as vitamin H or coenzyme R, is a water-soluble B vitamin. As a prosthetic group of various carboxylases, (+)-biotin plays an important role in the formation of reversible carboxyl groups and the transfer of CO2, and it is needed for the growth of the entire biological world. Its structural formula is as shown in formula I: Harris et al reported the total synthetic route of (±)-biotin for the first time in 1944 (J.Am.Chem.Soc.1944,66,1756.), this route is starting material with L-cystine, through Reduction, coupling, Claisen condensation and more than 13 steps were performed to obtain (±)-biotin with a total yield of about 10%. So far, there have been many total synthetic routes repor...

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Problems solved by technology

These methods all have the disadvantage of cumbersome operation, which limits their application.

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