Collective Synthesis of 4‐Hydroxy‐2‐pyridone Alkaloids and Their Antiproliferation Activities

Abstract

A collective synthesis of 4-hydroxy-2-pyridone alkaloids--specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C--has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 μM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.

A Concise and Efficient Total Synthesis of Militarinone D

“…This sole synthesis of the target, which employed a sequence that featured a Horner–Wadsworth–Emmons (HWE) olefination of a conjugated aldehyde with the pyridone β‐ketophosphonate, was accomplished in a total of 22 steps (longest linear sequence of 14 steps) and in 5 % overall yield from a known intermediate 4a. Recently, another synthesis of militarinone D has been reported by Liu and co‐workers 4b…”

Synthesis and Configuration of a p‐Aminoacetophenonic Acid Isolated from Endophyte of the Mangrove Plant Kandel candel

“…The OH group in 8 was mesylated with MsCl to give 9 , which was then treated with LiBH 4 to achieve concurrent deoxygenation at the C‐3 and reductive removal of the chiral auxiliary to afford the known alcohol 10 . Conversion of 10 into the corresponding aldehyde by Swern oxidation (DMSO/(COCl) 2 /Et 3 N) followed by condensation with the carbanion of 11 and elimination of the resulting OH after activation with MsCl furnished enone 12 .…”

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

“…The reaction of 138 and 140 under SMCR condtions in the presence of Pd(PPh 3 ) 4 and Na 2 CO 3 gave compound 141 that can be generally considered as a key intermediate for synthesis of pyridone alkaloids. In two steps including interactive preparation of homologous aldehydes with all‐ trans ‐polyene scaffold, and divergent conditions of aldol condensation of pyridone intermediate 141 and the homologous aldehydes, the desired natural products 127‐136 were obtained in satisfactory overall yield (Scheme ) …”