ABSTRACT
The total synthesis of dysoxylactam A, a novel 17-membered macrolactam with potent multi-drug-resistant reversing activities, has been achieved, starting from 4-pentene-1-al in a longest linear sequence of 17 steps and 9.5% overall yield. The key transformations consist of iterative aldol and ring-closing metathesis reactions for the construction of the stereochemically enriched polypropionate scaffold and the macrocycle, respectively.
Subject(s)
Lipopeptides/chemical synthesis , Aldehydes/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cyclization , Drug Resistance, Multiple, Bacterial , Esterification , Lipopeptides/chemistry , StereoisomerismABSTRACT
Kanamienamide is a novel enol ether containing enamide with a single digit micromolar inhibitory activity against cancer cell lines. An efficient and convergent total synthesis of kanamienamide has been developed for the first time, which features a Cu-mediated amide coupling with vinyl iodide at the late stage. Other key transformations include Evans asymmetric alkylation, CBS asymmetric reduction, ring-closing metathesis reaction, and Stork-Zhao-Wittig olefination. This strategy is amenable for facile analogue preparation and SAR studies.
Subject(s)
Amides/chemical synthesis , Ethers/chemical synthesis , Amides/chemistry , Ethers/chemistry , Molecular StructureABSTRACT
A unified modular synthetic strategy has been developed for the first total synthesis of dictyodendrins G and synthesis of dictyodendrin F, H and I in 11 steps. The synthesis features consecutive functionalization of the core aminoquinone by palladium-mediated Suzuki-Miyaura coupling reaction, 1,4-addition, acylation and base mediated formation of a pyrrolinone, and the formation of carbazolequinone moiety through a formal [3 + 2] cycloaddition using arynes generated in situ. Several dictyodendrin analogues were also synthesized using this strategy.