Natural product synthesis is one of the most creative branch of chemistry in terms of its boundless scope for innovation and has stimulated several generations of synthetic organic chemists. With advancement in the technology, particularly in the isolation and purification techniques, high-field NMR and X-ray crystallography, it has become fairly routine to isolate and assign the structures, high-field NMR and X-ray crystallography, it has become fairly routine to isolate and assign the structures, even to those complex molecules, which are available only in microscopic quantities from natural sources. Concurrently, one has witnessed tremendous advances in the availability of new synthetic methodologies with high region-, stereo-, and enantiocontrol for one or multiple C-C bond formations and rapid generation of molecular complexity. These developments have rekindled interest with total synthesis of natural products as platforms for testing and validating new reactions and strategies. Many natural products exhibit wide range of biological activities and thus provide good leads in drug discovery but quite often such bioactive compounds are obtained only in minute quantities from Nature. Hence, there is need to synthesize them to obtain requisite quantities and build diversity around their scaffold to further explore their therapeutic potential. Thus, natural product synthesis combines both intellectual challenge and possible application for human wellbeing. Our research group is actively engaged in the synthesis of structurally complex, bioactive natural products and as a part of this endeavour, total syntheses of several bioactive compounds have been accomplished in our laboratory in recent past. The present thesis has also evolved around the ongoing theme directed towards natural product synthesis and is organized under three chapters. Chapter I: Total synthesis of (+)-1S-Minwanenone Chapter II: Enantioselective total synthesis of the bioactive natural product (+)-Sch 642305. Chapter III: Enantiospecific total synthesis of 6-epi-(-)-Hamigeran B.

<p>The hamigeran diterpenoid is a family of natural products with diverse structures and biological activities. Most of the syntheses focus on hamigerans with [6–6–5] tricyclic core, but synthetic efforts toward the more challenging [6–7–5] tricyclic hamigerans are very limited. Herein, our studies in synthesizing the [6–7–5] tricyclic hamigerans are disclosed.  Through a benzyne-β-ketoester annulative ring expansion and a Nazarov reaction, an approach toward the [6–7–5] tricyclic carbon skeleton of the hamigeran natural products was developed. A Ni-catalyzed conjugate methyl addition or a Corey–Chaykovsky reaction installed the all-carbon quaternary center, and a Suzuki cross coupling followed by reduction introduced the isopropyl group. However, the reduction of challenging tetra-substituted double bond or the regio-selective cyclopropane opening was not successful despite multiple conditions were tried. A revised synthetic strategy was proposed and resulted in a convergent total synthesis of (±)-hamigeran M, enabled by five C–H functionalization reactions and proceeding in 11 steps in 3.9% overall yield. The C–H functionalizations include a hydroxy-directed C–H borylation, one C–H metalation-1,2-addition, one C–H metalation-Negishi coupling, a late-stage oxazole-directed C–H borylation-oxidation, and one electrophilic bromination. Further elaboration of the intermediates obtained here has delivered an advanced polysubstrituted precursor towards multiple other hamigerans.</p>