Asymmetric Total Synthesis of Biologically Active Natural Products Employing Chiral Catalysts

Abstract

We have described the enantioselective approaches for the synthesis of functionalized amino acids, 2-alkyl substituted tetrahydroquinoline, α-phenyl-β2-amino acid and 3-substituted pyrrolidines, along with their applications to the total synthesis of (R)-lacosamide, (+)-angustureine, (S)-nakinadine B and pyrrolidine core of serotonin norepinephrine reuptake inhibitors respectively employed Trost’s DYKAT, organocatalzyed-aminoxylation, Michael addition and Jacobsen’s HKR reactions as key steps. We have also developed a new stereocontrolled tandem organocatalyzed α-aminoxylation/Henry reaction approach for the asymmetric synthesis of dihydroxynitroalkanes from aldehydes and described its applications to the total synthesis of (-)-safingol. In addition to the above, we have also described two new different approaches for enantioselective total syntheses of (+)-disparlure, a lepidopteran sex pheromone via asymmetric organocatalysis. The merits of these synthetic approaches are high enantio- and diastereoselectivity with high yielding reaction steps. All the new compounds were characterized by 1H-NMR, 13C NMR, HRMS, %ee by chiral HPLC and [α]D25 for all new chiral compounds.