Bioorganic & Medicinal Chemistry Letters 2008-11-01

Piperidine dispiro-1,2,4-trioxane analogues.

Sunil Sabbani, Paul A Stocks, Gemma L Ellis, Jill Davies, Erik Hedenstrom, Stephen A Ward, Paul M O'Neill

Index: Bioorg. Med. Chem. Lett. 18(21) , 5804-8, (2008)

Full Text: HTML

Abstract

Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity.