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Total Synthesis and Antitrypanosomal Activity of Janadolide and Simplified Analogues
Jonathan H Chung1, Arthur H Tang1, Kieran Geraghty1
1School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
Abstract:
Janadolide is a cyclic depsipeptide natural product isolated from the marine cyanobacterium Okeania sp. Herein, we describe the total synthesis of janadolide, along with eight simplified analogues, via an efficient solid-phase strategy. Crucial to the synthesis of the natural product was the construction of a key polyketide fragment via an enantioselective (-)-B-chlorodiisopinocampheylborane-mediated reduction and a B-alkyl Suzuki reaction. Janadolide and the simplified analogues exhibited antitrypanosomal activity against pathogenic Trypanosoma brucei rhodesiense and Trypanosoma cruzi parasites.
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