Chemical synthesis study demonstrates a divergent pathway to (+)-kuhistanicaol G and (+)-ferutinin via jaeschkeanadiol, facilitating drug discovery for pancreatic cancer.
Motivated by the potent anticancer activity of kuhistanicaol G and ferutinin against the pancreatic cancer cell line PANC-1, we report the total syntheses of (+)-kuhistanicaol G and (+)-ferutinin. Our divergent synthetic strategy proceeds through the common intermediate jaeschkeanadiol and features several key transformations, including tandem radical addition/allylation, chelation-controlled nucleophilic addition, and Chugaev elimination. This work establishes a robust platform for the synthesis of structurally diverse analogues of (+)-kuhistanicaol G and (+)-ferutinin, as well as mechanistic chemical probes, thereby facilitating the future development of natural product-derived therapeutics for pancreatic cancer.
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Park et al. (2026) studied this question.
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