Preparation method, intermediate and preparation method of hexahydrofuro-furanol derivative

• Main Authors: WAN ZHIDONG, CHEN JIANHUA, ZHOU ZENGLE, MA XIAODONG, LIN JINGXIN, HE DAWEI, GAO ZHAOBO, XIANG WEI, MEI YIJIANG
• Format: Patent
• Language: Chinese; English
• Published: 12.05.2023
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HETEROCYCLIC COMPOUNDS; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

The invention relates to the field of medicine synthesis, in particular to a preparation method of a hexahydrofuro-furanol derivative, an intermediate of the hexahydrofuro-furanol derivative and a preparation method of the intermediate. According to the preparation method, a compound as shown in a formula A1 is used as a starting raw material, chirality is constructed through an enzymic method in the preparation process of the hexahydrofuro-furanol derivative, and the product with very high optical purity can be prepared by adopting the technical means. The preparation method can be used for commercially producing and preparing the darunavir key intermediate (3R, 3aS, 6aR)-hexahydrofuro [2, 3-b]-3-alcohol, and is a very economical route suitable for industrial production. 本发明涉及医药合成领域，具体涉及六氢呋喃并呋喃醇衍生物的制备方法、其中间体及其制备方法。该制备方法以式A1化合物为起始原料，在六氢呋喃并呋喃醇衍生物的制备过程中，通过酶法来构建手性，采用这样的技术手段能够非常高光学纯度制备得到产物。该制备方法能商业化生产制备达芦那韦关键中间体(3R,3aS,6aR)-六氢呋喃并[2,3-b]-3-醇，是一条非常经济，适合于工业化生产的路线。