Executive Summary : | The stereoselective synthetic routes of 22-membered diene macrolides dactylides (A-C) and 26-membered triene macrolides catenulisporolides (A-D) embedded with hydroxypyran hemiketal moiety, long-chain aliphatic polyol unit and macrocyclic lactone functionality have been projected. These bio-active secondary metabolites were discovered recently from rare actinomycetes, which act as the reservoir of promising bioactive metabolites. Dactylides (A-C) were isolated from Dactylosporangium aurantiacum (a Gram-positive soil-based actinobacteria) ATCC fermented broth through repeated chromatographic separation techniques and act as significant in-vitro antimycobacterial and cytotoxic metabolites. similarly, catenulisporolides (A-D) were extracted from the underexplored genera Catenulispora acidiphila, by slow growth laboratory culture which exhibit antimalarial resistivity against Plasmodium falciparum strains. structurally, both dactylides and catenulisporolides possess fourteen stereogenic centers. In addition, the presence of conjugated olefins, several adjacent 1,3-hydroxy groups, beta-hydroxy hemiketal core together with multiple glycoside linkages made these macrolides structurally complex and synthetically challenging. Amphotericin B, arachidonic acid metabolite hemiketal E2, and glycosylated lipiarmycin antibiotics such as fidaxomicin or tiacumicin are some of the structurally resembled macrolides, although, the total syntheses or any fragment of these polyketide dactylides and catenulisporolides are not known till the date. Here, we have proposed the logical total synthetic strategies applying asymmetric aldol reactions, Iridium-catalyzed crotylation, Yamaguchi esterification, Takai olefination, intramolecular Heck coupling as the key steps. The chemistry what is proposed would be executed in Prof. R. K. Goswami laboratory of Indian Association for the Cultivation of science, Kolkata as his laboratory one of the pioneering laboratories for such chemistry. Finally, the structure activity relationship (sAR) of the proposed dactylides and catenulisporolides will be carried out to understand the molecular basis of these natural products against different biological aspects. |