公开(公告)号：US20240199521A1

公开(公告)日：2024-06-20

申请号：US18275291

申请日：2022-01-19

Applicant: FUDAN UNIVERSITY

Inventor： Shengming MA ,  Weifeng ZHENG ,  Hui QIAN

IPC: C07C51/12 ,  B01J31/02 ,  B01J31/22 ,  B01J31/24 ,  C07C59/52

CPC classification number: C07C51/12 ,  B01J31/0259 ,  B01J31/2282 ,  B01J31/2428 ,  C07C59/52 ,  B01J2531/004 ,  B01J2531/0205 ,  B01J2531/824

Abstract: Disclosed in the present invention is a preparation method for a tetra-substituted allenoic acid compound based on a palladium catalytic system, that is, a highly optically active allenoic acid compound having axial chirality is directly constructed in one step by reacting tertiary propargyl alcohol, carbon monoxide and water in an organic solvent under the action of a palladium catalyst, a chiral bisphosphine ligand, an organophosphoric acid, and an organic additive, and the theoretical yield can reach 100%. The method of the present invention is simple to operate, the raw materials and reagents are readily available, the reaction conditions are mild, the substrate universality is wide, the functional group compatibility is good, the reaction has high enantioselectivity (77%˜96% ee), and the reaction is well compatible with complex natural products or substrates of a drug molecular skeleton. The highly optically active allenoic acid compound obtained by the present invention can be used as an important intermediate for constructing a γ-butyrolactone compound containing a tetra-substituted chiral quaternary carbon center, tetra-substituted allenol, tetra-substituted allenal, tetra-substituted allenyl ketone, tetra-substituted allenami de and other compounds.

公开(公告)号：US20240166597A1

公开(公告)日：2024-05-23

申请号：US18276365

申请日：2021-12-17

Applicant: FUDAN UNIVERSITY

Inventor： Shengming MA ,  Weiyi WANG ,  Yibo YU ,  Hui QIAN

IPC: C07C403/14 ,  C07C403/08 ,  C07C403/10 ,  C07C403/16 ,  C07C403/20

CPC classification number: C07C403/14 ,  C07C403/08 ,  C07C403/10 ,  C07C403/16 ,  C07C403/20

Abstract: Disclosed in the present invention is a total synthesis method for vitamin A and derivative thereof and deuterated compound thereof. β-cyclocitral is used as a starting material to produce alkenyl boronate, then the alkenyl boronate (or hydrolyzed alkenyl boric acid) is subjected to a series of reactions to produce retinal or retinal with substituent, and the retinal or retinal with substituent is further subjected to a reduction reaction to obtain vitamin A or vitamin A with substituent; the vitamin A or vitamin A with substituent is subjected to an esterification reaction to obtain vitamin A ester or vitamin A ester with substituent; or said retinal or retinal with substituent is subjected to an oxidation reaction to obtain vitamin A acid or vitamin A acid with substituent. When deuterated allenol is used, deuterated vitamin A and derivative thereof are obtained. The present invention has the advantages of short synthetic route, simple operation, readily available raw materials and reagents, and modularization and divergence, and can synthesize the deuterated vitamin A and derivative thereof which are difficult to synthesize in the prior art.

公开(公告)号：US20220064096A1

公开(公告)日：2022-03-03

申请号：US17299082

申请日：2019-12-24

Applicant: FUDAN UNIVERSITY

Inventor： Shengming MA ,  Weifeng ZHENG ,  Hui QIAN

IPC: C07C51/12 ,  C07B53/00 ,  C07C51/14

Abstract: The present invention discloses a method for directly constructing highly optically active tetrasubstituted allenic acid compounds, i.e., a one-step process for directly constructing highly optically active axially chiral tetrasubstituted allenic acid compounds by using tertiary propargyl alcohol, carbon monoxide and water as reactants in an organic solvent in the presence of palladium catalyst, chiral diphosphine ligand, monophosphine ligand and organic phosphoric acid. The method of the present invention has the following advantages: operations are simple, raw materials and reagents are readily available, the reaction conditions are mild, the substrate has high universality, the functional group has good compatibility, and the reaction has high enantioselectivity (90%˜>99% ee). The highly optically active allenic acid compounds obtained by the present invention can be used as an important intermediate to construct γ-butyrolactone compounds containing tetrasubstituted chiral quaternary carbon centers, tetrasubstituted allenic alcohol and other compounds.