Enantioselective Total Synthesis of Bioactive Compounds Employing Transition Metal Based Chiral Ligands and Organocatalysis

Abstract

Chapter1:Natural products have evolved over millions of years, possesses multi-dimensional chemical structures; which results in diversity in their biological activities and drug-like properties. Natural products will undergo continual use towards meeting the urgent need to develop effective drugs, and in turn play a noteworthy part in the discovery of therapeutic agents for curing human diseases. 1 Among the various techniques used to create analogues and derivatives of natural products, asymmetric synthesis by applying chiral auxiliary and new methodologies consisting of fewer steps and lesser cost, are of great significance. Catalytic asymmetric reactions provide a practical entry into the chiral world due to their economical use of asymmetry inducing agents. The osmium tetroxide-catalyzed Sharpless asymmetric dihydroxylation (AD) of olefins, embedding two hydroxyl groups in a hydrocarbon framework is perhaps one of the well-grounded and selective transformations in organic chemistry. Chapter2:The orexins (hypocretins)11 functions as neurotransmitter and widely participate in sleep regulations.12 This correlation demonstrated the use of Orexin receptors for the cure of sleep illness in place of sedative hypnotics that may cause unwanted side effects. Campeau and coworkers13a discovered a structurally distinct, dual Orexin Receptor Antagonists (DORA) named MK-6096 (Figure 1) that was under evaluation to be used as a potent drug for the treatment of insomnia. MK-6096 15, consist of trans-2,5 disubstituted piperidinyl core 16, a biaryl acid and fluoropyridine fragment. Chapter3:In the early 1990’s, Ksander and co-workers developed an active pharmaceutical compound Sacubitril (AUH-377) 31 which is a pro drug neprilysin inhibitor. 16a Combinations of Sacubitril 31 with the angiotensin II receptor-blocker Valsartan 32 by co-crystallization are known as supramolecular complex LCZ696 which was developed by Novartis for the treatment of heart failure (HF).17 A first-in-class combination drug LCZ696 (brand name Entresto) was approved by FDA in 2015 and is used to reduce the risk of cardiovascular death and hospitalization for HF in patients with reduced ejection fraction and chronic HF (NYHA Class II−IV). Chapter4:The novel decanolide compounds, cytospolide A-E (52-60) along with other thirteen natural product analogues (cytospolides F-Q and decytospolides A and B) were isolated by Zhang and co-workers from leaves of endophytic fungus shrub Ilex canariensis found mainly in the island of Gomera, Spain.23a,b A number of cytospolides showed cytotoxic effects to various human carcinoma cell lines. The C-2 methyl group inversion in cytospolide E 56 from 2R of 55 to 2S of 56 was found to lead to a surprise increase in cytotoxic activity against the A-549 tumor cell lines.