Antiproliferative Natural Products from the Madagascar Rainforest

Abstract

As part of an International Cooperative Biodiversity Groups (ICBG) program and a continuing search for anticancer natural products from the Madagascar rainforest, twenty extracts from Madagascar were selected for investigation based on their antiproliferative activity. Bioassay-guided fractionation of five of the extracts yielded sixteen new compounds, and their structures were determined using a combination of 1D and 2D NMR experiments, including COSY, HSQC/HMQC, HMBC, and ROESY/NOESY sequences, mass spectrometry, and chemical conversion. In addition, ten known compounds were obtained from five of the extracts. Studies on the remaining extracts were suspended due to various reasons. A multi-step synthesis of the sesquiterpenoid, (7R*)-opposite-4(15)-ene-1beta,7-diol, was also described. The first chapter of this dissertation reviews the new compounds isolated from Malagasy plants and marine organism in the last two decades. Chapters II to VI discuss the isolation, structure elucidation and bioactivities of new compounds from Scutia myrtina, Cordyla madagascariensis ssp. madagascariensis, Elaeodendron alluaudianum, Cassipourea lanceolata, and Sclerocarya birrea subsp. caffra. Chapter VII describes the synthesis and bioactivity of the sesquiterpenoid,(7R*)-opposite-4(15)-ene-1beta,7-diol. The isolation of known compounds is discussed briefly in the last chapter.