Stereoselective synthesis of functionalized allenes, total synthesis of monticolides A and B, and towards the total synthesis of tulearin C

Abstract

The thesis, entitled as “Stereoselective synthesis of functionalized allenes, Total synthesis of Monticolides A and B, and towards the total synthesis of Tulearin C” is divided into two chapters. Section A chapter-1 deals with the stereoselective synthesis of functionalized allenes from tartaric acid. Desymmetrization of the C-2 symmetric bis-dimethylamide derived from tartaric acid by addition of alkynyl Grignard / lithium reagents to yield the mono alkynyl ketones was achieved in good yield. Stereoselective Luche reduction of the mono alkynyl ketones furnished the corresponding alcohols which were transformed to allenes using Claisen rearrangement. Application of the allenes was demonstrated in the synthesis of the polyhydroxy unit of the natural product anamarine and in the synthesis of one of the THP units of the natural product sorangicin. (Part of this work has been published: Shruthi, K. S.; Singh, P.; Prasad, K. R. Tetrahedron 2020, 76, 131706). Section B of chapter-1 describes the total synthesis of monticolides A and B, -pyrone containing natural products. Key step in the synthesis include iridium catalysed redox reaction of the Achmatowicz reaction product obtained from the furyl carbinol. The furyl carbinol was obtained by elaboration of the bis-Weinreb amide. (Part of this work has been published: Singh, P.; Prasad, K. R. Tetrahedron, 2021, 84, 132004). Section C of chapter-1 is concerned with synthesis of the THF unit of the natural product trans-solamin from the bis-Weinreb amide derived from tartaric acid. Key step for the synthesis of the trans-THF unit is the cobalt catalysed Mukaiyama oxidative cyclization of the butenyl alcohol derived from bis-Weinreb amide. Boord olefination followed by olefin cross metathesis reaction/ hydrogeantion were employed for the synthesis of the intermediate, the conversion of which to trans-solamin is reported in literature, thus constituting a formal synthesis. Section D of chapter-1 of the thesis discloses the enantiodivergent synthesis of 2-epi-noviose from the bis-Weinreb amid. Pivotal steps in the synthesis include Wacker type oxidation reaction. Second chapter of the thesis describes the efforts towards the total synthesis of the macrolactone tulearin C. The synthesis of C3-C13 portion of tulearin C was accomplished from the allyl alcohol using Claisen rearrangement reaction. Alcohol was prepared which in turn was synthesized from the bis-Weinreb amide.