Total Synthesis Of Bio-Active Natural Products Microcarpalide, Synargentolide A, Jaspine B And Anamarine

Abstract

The thesis entitled “Total synthesis of bio-active natural products microcarpalide, synargentolide A, jaspine B and anamarine.” demonstrates the utility of chiral pool tartaric acid as the source in the synthesis of bio-active natural products. The thesis was divided into four sections. Section I of the thesis deals with the enantiodivergent synthesis of microcarpalide from tartaric acid. Microcarpalide is a 10-membered lactone of polyketide origin isolated from the fermentation broths of an unidentified endophytic fungi, found to be weekly cytotoxic to mammalian cells and acts as a microfilament discrupting agent. Stereoselective approach for the synthesis of ()-microcarpalide is described from D- and L-tartaric acids, while enantiodivergent approach for the synthesis of both enantiomers is described from L-tartaric acid using ring closing metathesis as the Scheme 2: Enantiodivergent total synthesis of microcarpalide. In section II of the thesis, stereoselective synthesis of synargentolide A is described. Synargentolide A is a polyhydroxy -lactone, isolated from Syncolostemon argenteus, which was founf to exhibit cytotoxic and antitumor properties. Stereoselective synthesis of synargentolide A was accomplished, starting from L-tartaric acid employing, Keck and Brown allylations and ring closing metathesis, as the key steps. Scheme 3: Stereoselective total synthesis of ()-synargentolide A. Section III of the thesis deals with the synthesis of ()-jaspine B. Pachastrissamine (jaspine B), is an anhydrophytoshingosine derivative, isolated from marine sponges Pachastrissa and Jaspis speces. Pachastrissamine was shown to exhibit cytotoxicity (IC 50 0.01 g/mL) against P388, A549, HT29, and MEL28 cell lines. Enantioselective synthesis of jaspine B is accomplished from L-tartaric acid employing, Keck allylation, acid mediated formation of tetrahydrofuran, and olefin cross metathesis as the key reactions. In section IV of the thesis, enantioselective synthesis of ()-anamarine is described. Anamarine is a polyhydroxy -lactone isolated from the flowers and leaves of Peruvian hyptis, possessing cytotoxicity against human tumor cell lines. Enantioselective synthesis of -anamarine is accomplishedelaboration of hitherto unknown -keto phosphonate derived from tartaric acid amide. In an appendix for the thesis, enantiodivergent synthesis for 4-siloxy-pent-2-enone was described. The usefulness of asymmetric aldol reaction is exemplifiedin this section. hydroxy amide synthesized from crotonaldehyde is suitably elaborated to the diene which on RCM yielded 4-silyloxycyclopent-2-enone. Further synthetic modification of this compound afforded the other enantiomer. Scheme 6: Enantiodivergent synthesis of hydroxy cyclopentenones. (For structural formula pl the abstract pdf file)