New Synthetic Methods and their Applications for Rapid Total Syntheses of Complex Natural Products and Bioactive Molecules

Project acronym:   New SMART Synthesis

Project type:   IDEJE

Grant agreement No.:   7750119

Project Web site:   https://newsmartsynthesis.rs/

Project is funded by:   Science Fund of the Republic of Serbia (Belgrade, Serbia)

Instituions where the research is conducted:

• University of Belgrade - Faculty of Chemistry (Belgrade, Serbia) – Coordination
• Innovation center of the Faculty of Chemisty in Belgrade (Belgrade, Serbia) – Beneficiary

Project realization is scheduled from January 24, 2022 till January 23, 2025.

Project staff

Short description of the project

Project NewSMARTSynthesis should bring cutting edge contributions to the art and science of organic synthesis, through both synthetic accomplishments and methodological developments. Important breakthroughs in strategy and tactics of organic synthesis should be demonstrated by innovative, unified, enantioselective total syntheses of several natural products currently designated as the most challenging synthetic targets: polycyclic, topologically and stereochemically complex diterpenes (e.g. waihoensene, conidiogenone B) and indole alkaloids (e.g. rauvomine B, alstonlarsine A). These compounds will be synthetized for the first time, or by syntheses considerably shorter (and more efficient), as compared to the current state of the art accomplishments. Important methodological breakthroughs are expected to bring about two novel methods for cyclization of vinyl radicals and unsaturated esters. This will be achieved by photoredox- and cooperative organo/photoredox catalysis, respectively, and aims at the development of a new generation catalysts integrating several functions within a single molecule.
The synthetic efforts should give rise to a number (a small library) of bioactive compounds, with a range of biological activities of interest for medicinal, pharmaceutical chemistry and chemical biology.
The impact of the proposed research would be multifaceted, of interest and relevance for researchers, teachers and students in the fields of organic synthesis, medicinal chemistry, and interdisciplinary fields. The Project results should represent the fundamental scientific contribution, durable and pertinent to the aforementioned research fields well after the Project termination. Potential applications involve synthesis of pharmaceuticals and agrochemicals.

Representative references

Z. Ferjancic, A. Kukuruzar, F. Bihelovic: Total Synthesis of (+)-Alstonlarsine A, Angewandte Chemie International Edition 2022, 61, e202210297. HIGHLIGHTED in SYNFACTS (2022, 11, 1168).

Z. Ferjancic, F. Bihelovic: Total Synthesis of (+)-Alstonlarsine A: Old Reactions in Modern Alkaloids Synthesis, Synlett 2023, 34, 203.

F. Djurkovic, Z. Ferjancic, F. Bihelovic: Intramolecular Dearomative Inverse-Electron-Demand Diels Alder Strategy for the Total Synthesis of (+)-Alstonlarsine A, Journal of Organic Chemistry 2023, 88, 11618.

Illustrations of research and results attained