Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent.

Abstract

A stereoselective and efficient method for free radical addition of benzyl thiol to aryl acetylene in the presence of Et3B-hexane has been developed for the synthesis of (Z) and (E)-styryl benzyl sulfides where base catalyzed hydrothiolations have failed. The scope of this reaction was successfully extended for the synthesis of (E)-ON 01910·Na, a phase III clinical stage anti-cancer agent and its inactive geometrical isomer (Z)-ON 01910·Na. It is interesting to note that all the E-isomers synthesized have shown better cytotoxicity profile on cancer cells compared to the Z-isomers.

• Authors: Venkat R Pallela, Muralidhar R Mallireddigari, Stephen C Cosenza, Balaiah Akula, D R C Venkata Subbaiah, E Premkumar Reddy, M V Ramana Reddy
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 11 Issue 12 Pg. 1964-77 (Mar 28 2013) ISSN: 1477-0539 [Electronic] England
• PMID: 23386308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Antineoplastic Agents
• Sulfhydryl Compounds
• Sulfones
• ON 01910
• Glycine

Topics

• Alkynes (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Clinical Trials, Phase III as Topic
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Glycine (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Humans
• K562 Cells
• Molecular Structure
• Stereoisomerism
• Structure-Activity Relationship
• Sulfhydryl Compounds (chemistry)
• Sulfones (chemical synthesis, chemistry, pharmacology)