公开(公告)号：US20220024949A1

公开(公告)日：2022-01-27

申请号：US17449509

申请日：2021-09-30

Applicant: The Scripps Research Institute

Inventor： Phil Baran ,  Chao Li ,  Jie Wang ,  Amab K. Chatterjee ,  Manoj Kumar ,  Shan Yu ,  Kristen Johnson ,  Tian Qin ,  Ming Shang

IPC: C07F5/02 ,  B01J31/02 ,  C07B47/00 ,  C07K7/64

Abstract: The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(II) salt or a copper salt, and an Mg(II) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.

公开(公告)号：US11161859B2

公开(公告)日：2021-11-02

申请号：US16495907

申请日：2018-03-14

Applicant: The Scripps Research Institute

Inventor： Phil Baran ,  Chao Li ,  Jie Wang ,  Arnab Kumar Chatterjee ,  Manoj Kumar ,  Shan Yu ,  Kristen Ann Johnson ,  Tian Qin ,  Ming Shang

IPC: C07F5/02 ,  B01J31/02 ,  C07B47/00 ,  C07K7/64

Abstract: The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(ll) salt or a copper salt, and an Mg(ll) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.

公开(公告)号：US20200024290A1

公开(公告)日：2020-01-23

申请号：US16495907

申请日：2018-03-14

Applicant: The Scripps Research Institute

Inventor： Phil Baran ,  Chao Li ,  Jie Wang ,  Arnab Kumar Chatterjee ,  Manoj Kumar ,  Shan Yu ,  Kristen Ann Johnson ,  Tian Qin ,  Ming Shang

IPC: C07F5/02 ,  C07B47/00 ,  B01J31/02 ,  C07K7/64

Abstract: The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(11) salt or a copper salt, and an Mg(11) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.