Chemical Science 2013-07-01

A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the interrupted Ugi reaction.

Jimin Kim, JohnS Schneekloth, ErikJ Sorensen

Index: Chem. Sci. 3(9) , 2849-2852, (2012)

Full Text: HTML

Abstract

A synthesis of 11-methoxy mitragynine pseudoindoxyl, a new member of the mitragynine class of opioid agonists, from a derivative of the Geissman-Waiss lactone is described. An internal attack of an electron-rich aromatic ring on an electrophilic nitrilium ion and a late-stage construction of the functionalized piperidine ring by the method of reductive cyclization are the pivotal transformations; both ring annulations proceed in a highly diastereoselective fashion. The construction of substituted indoxyl frameworks by the interrupted Ugi method offers an attractive alternative to the strategy of oxidatively rearranging indoles.