European Journal of Biomedical and Pharmaceutical Sciences

ADVANCEMENTS IN THE TOTAL SYNTHESIS OF CYCLOTRIPEPTIDIC NATURAL PRODUCTS: EXPLORING THE THERAPEUTIC POTENTIAL OF MARINE-DERIVED COMPOUNDS

Alma Soudan, Joudy Abokassem, Shaam Ammar and Nasser Thallaj*

ABSTRACT

The exploration of marine natural products has garnered significant interest due to their unique chemical diversity and potential therapeutic applications. This document focuses on the total synthesis of cyclotripeptidic natural products, particularly those within the aurantiomide series, which contain the piperazino[2,1-b]quinazolin-3,6-dione core structure. These compounds exhibit notable pharmacological properties, including anticancer, anti-inflammatory, and antimicrobial activities. The synthesis of these complex molecules has historically faced challenges related to their intricate structures and biosynthetic pathways. Recent advancements in synthetic methodologies, such as microwave-assisted synthesis and biomimetic oxidation, have enhanced the efficiency and selectivity of these reactions. Additionally, innovative approaches like retro-Claisen rearrangements and late-stage functionalization have provided new strategies for generating cyclotripeptides with desired bioactivities. Despite these advancements, optimizing reaction conditions and improving yields remain ongoing challenges. This document also addresses the biosynthetic pathways of piperazino[2,1-b]quinazolin-3,6-dione cyclotripeptides, providing insights into the enzymatic processes that facilitate their formation. By highlighting both the synthetic strategies and the biological significance of these compounds, this work contributes to the growing body of knowledge surrounding marine natural products. Ultimately, continued exploration in this field aims to harness the therapeutic potential of marine biodiversity for future medicinal applications, paving the way for innovative drug discovery and development.

Keywords: Cyclotripeptides; Marine Natural Products; Piperazino[2,1-b]quinazolin-3,6-dione; Total Synthesis; Pharmaceutical Applications; Biosynthetic Pathways; Microwave-Assisted Synthesis; Oxidative Functionalization.