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Human pancreatic cancer cell lines are known for their inherent tolerance to nutrition starvation, which enables them to survive under a hypovascular (austerity) tumor microenvironment. The search for agents that preferentially retard the survival of cancer cells under low nutrition conditions (antiausterity agent) is a novel approach to anticancer drug discovery. In this study, it was found that a dichloromethane extract of the stem of Uvaria dac preferentially inhibited PANC-1 human pancreatic cancer cells survival under nutrition-deprived conditions at a concentration of 10 μg/mL. Workup of this bioactive extract led to the discovery of (+)-grandifloracin (8) as a potent antiausterity agent as evaluated in a panel of four human pancreatic cancer cell lines, PANC-1 (PC(50), 14.5 μM), PSN-1 (PC(50), 32.6 μM), MIA PaCa-2 (PC(50), 17.5 μM), and KLM-1 (32.7 μM). (+)-Grandifloracin (8) has been isolated from a natural source for the first time. Its absolute stereochemistry was established by single-crystal X-ray crystallography and circular dichroism spectroscopic analysis. In addition to this, seven other new highly oxygenated cyclohexene derivatives, named uvaridacanes A (1) and B (2), uvaridacols A-D (3, 4, 6, 7), and uvaridapoxide A (5), were also isolated and structurally characterized.

We herein report the synthesis of 2‐(2‐methoxyphenyl)‐1‐azaazulene (8) by a Suzuki–Miyaura cross‐coupling reaction between 2‐chloro‐1‐azaazulene and 2‐methoxyphenylboronic acid and also by the condensation of tropone and the ylide derived from 1‐(o‐methoxyphenacyl)pyridinium iodide. Demethylation of 8 afforded the title compound 6. X‐ray crystallographic analysis of 6 provided evidence for an intramolecular hydrogen bond between the phenolic hydrogen atom and the nitrogen atom of the azaazulenyl ring and also revealed its coplanar ring system. We also report the acidity, basicity, and absorption and emission behavior of 6.

14π‐Electrocyclization across the two pentafulvenoid moieties of pentafulvene 1 occurs upon heating to provide dicyclopenta[a,d]cyclooctene 2 [Eq. (1)]. The nonalternant hydrocarbon 2 shows diatropic character and a distinctive absorption spectrum with the longest wavelength maximum at 767 nm.

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