Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

Jian-bo Xie; Jian Luo; Timothy R. Winn; David B. Cordes; Guigen Li

doi:10.3762/bjoc.10.69

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

Jian-bo Xie, Jian Luo, Timothy R. Winn, David B. Cordes, Guigen Li^*

^*Corresponding author for this work

Research output: Contribution to journal › Letter › peer-review

Abstract

A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

Original language	English
Pages (from-to)	746-751
Number of pages	6
Journal	Beilstein Journal of Organic Chemistry
Volume	10
DOIs	https://doi.org/10.3762/bjoc.10.69
Publication status	Published - 31 Mar 2014

Keywords

Asymmetric borylation
GAP chemistry
Organophosphorous
N-phosphinylimine
Velcade
Imine chemistry
Boronic acids
Amino-acids
Chymotrypsin
Inhibitors
Elastase
Esters
Hydroboration
Aldehydes
Reagents

Access to Document

10.3762/bjoc.10.69

Cordes_2014_BJ_Group
© 2014 Xie et al; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc)
Final published version, 435 KB

Cite this

@article{b745bbac51804affb4cd33c0981b81cc,

title = "Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines",

abstract = "A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.",

keywords = "Asymmetric borylation, GAP chemistry, Organophosphorous, N-phosphinylimine, Velcade, Imine chemistry, Boronic acids, Amino-acids, Chymotrypsin, Inhibitors, Elastase, Esters, Hydroboration, Aldehydes, Reagents",

author = "Jian-bo Xie and Jian Luo and Winn, {Timothy R.} and Cordes, {David B.} and Guigen Li",

note = "The authors acknowledge the financial support from the NIH (R33DA031860), the Robert A. Welch Foundation (D-1361) and the Jiangsu Innovation Team Program (P. R. China) for their support of this research. They also thank NSF Grant CHE-1048553 and the CRIF program for supporting their NMR facility.",

year = "2014",

month = mar,

day = "31",

doi = "10.3762/bjoc.10.69",

language = "English",

volume = "10",

pages = "746--751",

journal = "Beilstein Journal of Organic Chemistry",

issn = "1860-5397",

publisher = "Beilstein-Institut Zur Forderung der Chemischen Wissenschaften",

}

TY - JOUR

T1 - Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

AU - Xie, Jian-bo

AU - Luo, Jian

AU - Winn, Timothy R.

AU - Cordes, David B.

AU - Li, Guigen

N1 - The authors acknowledge the financial support from the NIH (R33DA031860), the Robert A. Welch Foundation (D-1361) and the Jiangsu Innovation Team Program (P. R. China) for their support of this research. They also thank NSF Grant CHE-1048553 and the CRIF program for supporting their NMR facility.

PY - 2014/3/31

Y1 - 2014/3/31

N2 - A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

AB - A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

KW - Asymmetric borylation

KW - GAP chemistry

KW - Organophosphorous

KW - N-phosphinylimine

KW - Velcade

KW - Imine chemistry

KW - Boronic acids

KW - Amino-acids

KW - Chymotrypsin

KW - Inhibitors

KW - Elastase

KW - Esters

KW - Hydroboration

KW - Aldehydes

KW - Reagents

U2 - 10.3762/bjoc.10.69

DO - 10.3762/bjoc.10.69

M3 - Letter

SN - 1860-5397

VL - 10

SP - 746

EP - 751

JO - Beilstein Journal of Organic Chemistry

JF - Beilstein Journal of Organic Chemistry

ER -

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

Abstract

Keywords

Access to Document

Fingerprint

Cite this