Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors

Anthony D. William; Angeline C.-H. Lee

doi:10.2533/chimia.2015.142

Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors

Authors

Anthony D. William S*BIO Pte Ltd, 250 North Bridge Road, #28-00 Raffles City Tower, Singapore 179101; Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology, and Research (A*STAR), 11 Biopolis Way, Helios Block, #03-08, Singapore 138667, Singapore. wanthony11@gmail.com
Angeline C.-H. Lee S*BIO Pte Ltd, 250 North Bridge Road, #28-00 Raffles City Tower, Singapore 179101

DOI:

https://doi.org/10.2533/chimia.2015.142

Keywords:

Cyclin-dependent kinases (cdks), Grubbs catalyst, Janus kinase 2 (jak2), Ring closing metathesis (rcm), Zhan-1b catalyst

Abstract

The powerful olefin metathesis reaction was employed for the construction of late-phase clinical agents SB1317 and SB1518. In both cases RCM seems to proceed only in the presence of an acid and to predominantly furnish trans isomers. In case of SB1518 it proceeded in the presence of acid HCl, while for SB1317, it mainly proceeds in the presence of TFA (trifluroacetic acid).