PMID: 11929256Apr 4, 2002Paper

Synthesis, properties, and reactivity of cocaine benzoylthio ester possessing the cocaine absolute configuration

Journal of the American Chemical Society
Shigeki IsomuraK D Janda

Abstract

One aspect of immunopharmacotherapy for cocaine abuse involves the use of a catalytic monoclonal antibody (mAb) to degrade cocaine via hydrolysis of the benzoate ester. A cocaine benzoylthio ester analogue provides a means to implement high-throughput selection strategies to potentially isolate mAbs with high activity. The required analogue was synthesized starting from (-)-cocaine hydrochloride and possessed the cocaine absolute configuration. Key points in the preparation were the introduction of the sulfur atom at C-3 via a bromomagnesium thiolate addition to the exo face of anhydroecgonine, separation of C-2 diastereomers, recycling of a C-2 thio ester byproduct, and formation of the necessary C-2 methyl and C-3 benzoylthio esters. Effects resulting from the lower electronegativity and greater hydrophobicity of sulfur compared to oxygen were observed. These characteristics could result in interesting drug properties. Furthermore, the analogue was found to be a substrate for catalytic mAbs that hydrolyze cocaine as monitored by HPLC and also spectrophotometry by coupling cleavage of the benzoylthio ester to the disulfide exchange with Ellman's reagent. Screening antibody libraries with the new cocaine analogue using the spec...Continue Reading

References

Apr 1, 1979·Analytical Biochemistry·P W RiddlesB Zerner
Apr 1, 1979·Clinical Pharmacology and Therapeutics·D J StewartW Kalow
Mar 20, 1992·Journal of Medicinal Chemistry·J GubinP Chatelain
Apr 1, 1990·The American Journal of Medicine·S L BrodyK D Wrenn
Sep 1, 1989·Archives of Neurology·D C KlonoffW G Obana
Aug 11, 1989·Science·D C Des Jarlais, S R Friedman
Mar 1, 1983·Journal of Pharmaceutical Sciences·H N Bockbrader, R H Reuning
Feb 1, 1995·Journal of Clinical Psychopharmacology·N W WithersJ C Gillin
Mar 26, 1993·Science·D W LandryT M Georgiadis
Jan 1, 1996·Annual Review of Public Health·J W Cornish, C P O'Brien
Oct 1, 1996·Nature Medicine·D E HughesB F Boyce
Jun 4, 1998·Journal of Neuroimmunology·K GoodkinA M Kumar
Oct 10, 1998·The Journal of Membrane Biology·H FischerA Seelig
Feb 24, 2001·Bioorganic & Medicinal Chemistry Letters·M MatsushitaK D Janda
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN

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Citations

Jul 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·M Rocio A CarreraKim D Janda
Feb 4, 2012·Future Medicinal Chemistry·Charles W Schindler, Steven R Goldberg
Feb 27, 2003·Journal of the American Chemical Society·Chang-Guo ZhanDonald W Landry
May 1, 2013·Journal of Medicinal Chemistry·Xiaoqing CaiKim D Janda
Jun 15, 2005·Expert Opinion on Biological Therapy·Tobin J DickersonKim D Janda
Nov 9, 2010·Biophysical Chemistry·Guodong Hu, L Y Chen
Nov 7, 2006·Journal of Molecular Biology·Kathleen M McKenzieKim D Janda
Sep 25, 2004·Bioorganic & Medicinal Chemistry·Yang XuKim D Janda
Sep 8, 2004·Bioorganic & Medicinal Chemistry·M Rocío A CarreraKim D Janda

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