Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

Abstract

2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.

Harnessing alcohols as sustainable reagents for late-stage functionalisation: synthesis of drugs and bio-inspired compounds

“…[3][4][5] Therefore, designing a secure, affordable and environmentally benign roadmap for the production of APIs (active pharmaceutical ingredients) or drug-like molecules has attracted significant attention in synthetic organic chemistry and from researchers. 6 Traditionally, the total synthesis of pharmaceutically active molecules or natural product derivatives [7][8][9] and methodology development [10][11][12] enriched the synthetic strategies and the construction of bio-active molecules. However, due to the increase in the number of catastrophic diseases (such as SARS-COVID) worldwide, 13,14 the use of innovative techniques for manufacturing pharmaceuticals or drug derivatives has been gaining increasing attention.…”

“…However, due to the increase in the number of catastrophic diseases (such as SARS-COVID) worldwide, 13,14 the use of innovative techniques for manufacturing pharmaceuticals or drug derivatives has been gaining increasing attention. [7][8][9][10][11][12][15][16][17][18][19] Notably, Bruke published two reviews on automation techniques for synthesising various small molecules with biological potential using MIDA (N-methyliminodiacetic acid) boronate as a crosscoupling reagent. 20,21 Recently, Waldmann also documented and highlighted the synthetic potential of natural product-like molecules towards drug development.…”

“…Traditionally, the total synthesis of pharmaceutically active molecules or natural product derivatives 7–9 and methodology development 10–12 enriched the synthetic strategies and the construction of bio-active molecules. However, due to the increase in the number of catastrophic diseases (such as SARS-COVID) worldwide, 13,14 the use of innovative techniques for manufacturing pharmaceuticals or drug derivatives has been gaining increasing attention.…”

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

“…12 The field of asymmetric hydrogenation has developed rapidly since the introduction of research by Knowles and Sabacky 13 and Horner et al, 14 who initiated the development of homogeneous asymmetric hydrogenation using modified Wilkinson catalysts 15 in the late 1960s.…”