Over the past two decades and continuing on, carbonyl allylation chemistry has been a very useful and popular tool for the stereocontrolled formation of carbon-carbon bonds in the field of organic synthesis. In the context of natural product synthesis, the efficiency and status of aldehyde allylboration method is only matched by the asymmetric and diastereoselective aldol methodology. Unfortunately, prior to the new millennium, the means to control the absolute stereoselectivity in the addition of allylic boron reagents had been restricted to stoichiometric chiral directors, appended onto the metal center. In 2002, the research groups of Hall and Miyaura reported a new Lewis acid-catalyzed allylboration reaction manifold, which raised intriguing mechanistic questions and also paved the way for a catalytic enantioselective methodology development. Chapter 2 of this thesis details mechanistic studies related to the new Lewis acid-catalyzed allylboration. In this chapter, various control experiments and kinetic studies are presented, the results of which allowed us to propose a hypothesis involving the electrophilic boronate activation as the key factor for the observed rate enhancement. Chapter 3 describes the initial phase of our research to develop a catalytic enantioselective allylboration methodology. We discovered that Brnsted acid catalysts derived from diolSnCl4 complexes were promising catalysts for the asymmetric addition of air and moisture stable and commercially available allylic pinacol boronates. Under this 1st generation catalyst-system, the corresponding homoallylic alcohols were obtained in moderate to good enantioselectivity and excellent diastereoselectivity. The development of a novel chiral Brnsted acid catalyst for the highly enantio- and diastereoselective allylboration reaction methodology is the single most important result to come from this thesis. Chapter 4 outlines the development of the 2nd generation catalyst system. A systematic study of the diol component of the catalyst system led us to arrive at a novel diol nicknamed Vivol on behalf of my contribution. The resulting Brnsted acid derived from VivolSnCl4 now provided the corresponding homoallylic alcohol products in very good to excellent enantioselectivity. Preliminary mechanistic studies along with the X-ray diffraction structure of the catalyst system are also presented. Based on this information, an even better performaning diol (termed F-Vivol) was developed. This 3rd generation catalyst system derived from F-VivolSnCl4 complex was shown to display consistently superior reactivity and selectivity over its 2nd generation predecessor. Chapter 5 describes our efforts to expand the reagent scope of the Brnsted acid catalyzed allylboration methodology. Furthermore, this chapter also describes the successful application of the catalytic process towards the synthesis of simple and complex molecules. Accordingly, the preparation and application of the Brnsted acid-catalyzed addition of 2-bromoallyl boron pinacolate is described. The successful transformation of the corresponding bromo-homoallylic alcohols to a compelling class of -butyrolactones is also presented. The later part of the Chapter presents the synthesis of natural products (+) dodoneine and palmerolide A.

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The thesis entitled “Total synthesis of palmerolide A, dihydroconduritols and lentiginosine” is divided into two chapters. First chapter of the thesis describes the formal total synthesis of bioactive marine macrolide palmerolide A. Palmerolide A was isolated by Baker and co-workers from an Antarctic tunicate Synoicum adareanum. Palmerolide A is a 20-membered macrolactone containing five chiral centers and seven unsaturations. Palmerolide A was found to be potent and selectively cytotoxic against human melanoma cancer cell lines and was also shown to inhibit vacuolar V-ATPase. In section A, enantioselective formal total synthesis of palmerolide A is described. key steps in the synthesis involve Jung non-aldol aldol reaction to construct the C16-C23 fragment 1 and oxidation of a chiral furyl carbinol to assemble the C1-C15 fragment 2. Scheme 1: Synthesis of C16-C23 fragment of palmerolide A. Scheme 2: Formal total synthesis of palmerolide A In section B, enantiospecific formal total synthesis of palmerolide A is presented from chiral pool tartaric acid. This approach is based on coupling of the three fragments viz. C1-C8 enoic acid fragment 3, C9-C15 vinyl stannane fragment 4 and the C16-C23 vinyl iodide fragment 1. The C1-C8 enoic acid fragment 3 is synthesized from L-threotol obtained from L-tartaric acid, while synthesis of the C9-C15 fragment 4 involved the elaboration of a γ-hydroxy amide derived from the bis-Weinreb amide of tartaric acid. Stille coupling of the vinyl iodide 1 obtained by Jung non-aldol aldol process with the vinyl stannane 4 delivered the C9-C23 unit. Esterification of this unit with the enoic acid 3 followed by zinc mediated Boord olefination and RCM furnished the macrolactone which is further elaborated to palmerolide A. Scheme 3: Synthesis of C1-C8 fragment of palmerolide A. Scheme 4: Enantiospecific formal total synthesis of palmerolide A. Section A of the second chapter deals with the enantiospecific synthesis of dihydroconduritols E and F from tartaric acid. Conduritols are 1,2,3,4-cyclohex-5-ene tetrols and are shown to be inhibitors of glycosidase. A number of derivatives of conduritols were found to possess various biological activities. Enantiospecific synthesis of dihydroconduritol E and F is accomplished from tartaric acid employing the Boord type fragmentation and ring closing metathesis as the key steps. Scheme 5: Enantiospecific synthesis of dihydroconduritols E and F Section B of the second chapter describes the enantiospecific total synthesis of ()lentiginosine. Lentiginosine is a dihydroxylated indolizidine alkaloid isolated from leaves of the plant Astragalus lentiginosus. Lentiginosine is the most powerful and competitive inhibitor (IC50 5µg/mL) of amyloglucosidase known so far. Key transformation in the synthesis include the in situ reduction and cyclization of a dihydroxyazide derived from the γ-hydroxy amide prepared from tartaric acid amide. (for structural formula pl see the abstract file.)

Synoicum adareanum is a colonial tunicate commonly found on the benthos around Palmer Station on Anvers Island, Antarctica. A comprehensive chemical investigation of the lipophilic extract of the frozen tunicates gave a new series of polyketide macrolides, palmerolides A-E and H. The structure elucidation of these compounds was accomplished by extensive NMR and mass spectral studies.The palmerolides are unusual 20-membered macrolides displaying functionality more commonly found in sponges or cyanobacteria. Palmerolide A, the major member of the group, shows significant and selective in vitro cytotoxicity against melanoma with three orders of greater sensitivity relative to other cell lines tested, in the National Cancer Institute (NCI) 60 human cancer cell-line panel. In addition, it displays potent cytostatic activity against several other cancer cell lines. Based on NCI's COMPARE analysis, palmerolide A was investigated as a V-ATPase inhibitor and shown to bind the V0 subunit with 2 nM inhibition.Austrodoris kerguelenensis is a common Antarctic nudibranch widely distributed in the High Antarctic and Sub Antarctic Zone. It is characterized by the presence of terpenoid glyceryl esters which are supposed to be involved in defense. Chemical investigations of several specimens of A. kerguelenensis collected near Palmer station Antarctica afforded hitherto undescribed series of clerodane diterpenoid glycerides. The structure elucidation of three major compounds of this series, palmadorin A, B and C was accomplished.

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