ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Spirocyclisation of phytoalexin 1-methoxybrassinin in the presence of Grignard reagents

Peter Očenáš, Lucia Tomášová, Peter Kutschy, Pavel Pazdera, Ján Mojžiš, and Martina Pilátová

Department of Organic Chemistry, Institute of Chemical Science, Faculty of Science, P. J. Šafárik University, Moyzesova 11, 040 01, Košice, Slovakia

E-mail: peter.ocenas@gmail.com

Abstract: The anti-cancer properties of naturally occurring (2R, 3R)-(−)-1-methoxyspirobrassinol methyl ether (I) and their synthetic amino or piperidyl analogues II inspired us to study the synthesis of new target compounds III with a C—C bond in the 2-position of indole rather than a C—N or C—O bond (I or II respectively). The goal was achieved via electrophilic-nucleophilic 3,2-difunctionalisation of 1-methoxybrassinin (IV) in the presence of bromine and the Grignard reagent leading to the formation of cis- and trans-C—C analogues of I. Finally, the anti-cancer activities of the new compounds were measured and compared with I and II in order to show the importance of a heteroatom in the 2-substituted indole on the anti-cancer activity of spirobrassinols.

Keywords: phytoalexins – spirocyclisation – Grignard addition – spiroindolines – anti-proliferative activity

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-013-0335-7

Chemical Papers 67 (6) 631–642 (2013)