公开(公告)号：US20180340196A1

公开(公告)日：2018-11-29

申请号：US15871039

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Zedu HUANG ,  Ge MENG ,  Minjie LIU ,  Zhining LI ,  Zexu WANG ,  Haihui PENG ,  Fangjun XIONG ,  Yan WU ,  Yuan TAO

IPC: C12P7/62 ,  C07C69/732 ,  C07C67/28 ,  C12N9/04

CPC classification number: C12P7/62 ,  C07C67/28 ,  C07C69/732 ,  C12N9/0006 ,  C12Y101/0108 ,  G01N30/7206 ,  G01N30/88 ,  G01N2030/025

Abstract: The present disclosure relates to the technical field of biochemical engineering and particularly discloses a preparation method for (R)-3-hydroxyl-5-hexenoate. In the method of the present disclosure, the (R)-3-hydroxyl-5-hexenoate is prepared by catalytic reduction of 3-carbonyl-5-hexenoate by ketoreductase with 3-carbonyl-5-hexenoate as the substrate. The amino acid sequence of ketoreductase is shown in SEQ ID NO.1. In the present disclosure, the (R)-3-hydroxyl-5-hexenoate having a very high chiral purity is obtained by asymmetric reduction by ketoreductase as the biocatalyst. The present disclosure has the advantages of easy operation, mild reaction conditions, high reaction yield and good practical industrial application value.

公开(公告)号：US20180339974A1

公开(公告)日：2018-11-29

申请号：US15871049

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Guanxin HUANG ,  Ge MENG ,  Minjie LIU ,  Yan WU ,  Dang CHENG ,  Zedu HUANG ,  Haihui PENG ,  Fangjun XIONG

IPC: C07D319/06 ,  C07B41/12 ,  C07B47/00

CPC classification number: C07D319/06 ,  C07B41/12 ,  C07B47/00

Abstract: The present disclosure belongs to the technical field of organic synthesis and particularly relates to a preparation method for 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate. The 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is a key chiral intermediate for preparation of statin antilipemic agents. In the present disclosure, the 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is obtained by bromination and cyclization of 3-((substituted oxycarbonyl)oxy)-5-hexenoate as raw material with hypochlorite and bromide in an organic solvent in the presence of CO2. The method of the present disclosure has the advantages of readily available raw material, mild reaction conditions, easy operation, low cost, excellent atomic economy and less by-products, and is applicable to industrial production.

公开(公告)号：US20170183314A1

公开(公告)日：2017-06-29

申请号：US15038973

申请日：2014-01-10

Applicant: FUDAN UNIVERSITY

Inventor： FENER CHEN ,  Fangjun XIONG ,  Jie LI ,  Pingping ZHAN ,  Lingjun XU ,  Qiuqin HE ,  Wenxue CHEN ,  Xiayun Huang ,  Yan WU

IPC: C07D239/42

CPC classification number: C07D239/42 ,  A61K31/505

Abstract: The present invention belongs to the technical field of organic chemistry, and specifically relates to a method for preparing rosuvastatin sodium. The method of the invention comprises: reducing 4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimidine-5-carboxylic acid (VII) in the presence of a borohydride, an alkyl-substituted chlorosilane and an assistance in an organic solvent to prepare 4-p-fluorophenyl-5-hydroxymethyl-6-isopropyl-2-(N-methyl-methylsulfonylamino) pyrimidine (VIII); then performing a reaction of the compound VIII with a triphenyl phosphonium salt in an organic solvent to prepare a ((4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)-5-pyridyl)-methyl)triphenyl phosphonium salt (IX); performing a stereoselective Michael addition reaction of (S)-trans-4,5-dihydroxy-pent-2-olefine acid ester (II) with furfural (III) to prepare a 2-((4R,6S)-2-(furan-2-yl)-6-hydroxymethyl-1,3-dioxane-4-yl)acetate (IV); oxidizing the compound IV to prepare a 2-((4R,6S)-2-(furan-2-yl)-6-formacyl-1,3-dioxane-4-yl)acetate (V); performing an olefination reaction of the compound V with the (4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimid-5-yl)-methyl triphenyl substituted phosphonium salt (IX) or phosphate to prepare 2-((4R,6S)-6-(trans-2-(4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimid-5-yl)vinyl)-2-(furan-2-yl)-1,3-dioxane-4-yl)acetate (VI); and performing deprotection and sodium salt formation of compound VI to prepare rosuvastatin sodium (I). The method has easily obtainable raw materials, and is simple to operate and suitable for industrial productions.