An unusual Michael-induced skeletal rearrangement of a bicyclo[3.3.1]nonane framework of phloroglucinols to a novel bioactive bicyclo[3.3.0]octane

Veroniki P Vidali; Kornilia P Mitsopoulou; Marianna Dakanali; Konstantinos D Demadis; Andreani D Odysseos; Yiota A Christou; Elias A Couladouros

doi:10.1021/ol4020909

An unusual Michael-induced skeletal rearrangement of a bicyclo[3.3.1]nonane framework of phloroglucinols to a novel bioactive bicyclo[3.3.0]octane

Org Lett. 2013 Nov 1;15(21):5404-7. doi: 10.1021/ol4020909. Epub 2013 Oct 11.

Authors

Veroniki P Vidali¹, Kornilia P Mitsopoulou, Marianna Dakanali, Konstantinos D Demadis, Andreani D Odysseos, Yiota A Christou, Elias A Couladouros

Affiliation

¹ Synthesis and Bioorganic Chemistry, NCSR "Demokritos" , 153 10 Ag. Paraskevi, Athens, Greece, Chemical Laboratories, Agricultural University of Athens , Iera Odos 75, 118 55, Athens, Greece, Crystal Engineering, Growth & Design Laboratory, Department of Chemistry, University of Crete , P.O. Box 2208, GR-71003 Heraklion, Crete, Greece, EPOS-Iasis, R&D , 5 Karyatidon Street, 2028, Nicosia, Cyprus, and University of Cyprus , 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus.

PMID: 24117171
DOI: 10.1021/ol4020909

Abstract

A novel skeletal rearrangement of bicyclo[3.3.1]nonane-2,4,9-trione (16) to an unprecedented highly functionalized bicyclo[3.3.0]octane system (17), induced by an intramolecular Michael addition, is presented. This novel framework was found to be similarly active to hyperforin (1), against PC-3 cell lines. A mechanistic study was examined in detail, proposing a number of cascade transformations. Also, reactivity of the Δ(7,10)-double bond was examined under several conditions to explain the above results.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkanes / chemistry*
Bridged Bicyclo Compounds / chemistry*
Molecular Structure
Octanes / chemistry*
Phloroglucinol / chemistry*
Stereoisomerism

Substances

Alkanes
Bridged Bicyclo Compounds
Octanes
Phloroglucinol
nonane
octane