the C-C bond in the macrocycle. The McMurry synthesis uses a titanium-catalyzed carbonyl coupling reaction; the Takahashi synthesis uses intramolecular alkylation of an allyl halide by a protected cyanohydrin anion; the Suginome synthesis utilizes a geranyl fragment; and the de Groot synthesis synthesizes humulene from a crude distillate of eucalyptus oil. Humulene can also be synthesized using a combination of four-component assembly and palladium-mediated cyclization, outlined below. This synthesis is noteworthy for the simplicity of the C−C bond constructions and cyclization steps, which it is believed will prove advantageous in the synthesis of related polyterpenoids. To understand humulene's regioselectivity, the fact that one of the two triply substituted C═C double bonds is significantly more reactive, its conformational space was explored computationally and four different conformations were identified. Research In laboratory studies, humulene is being studied for potential anti-inflammatory effects. In 2015 researchers in Brazil identified α-Humulene as an active contributor to the insect repellent properties of commiphora leptophloeos leaf oil, specifically against “the yellow fever mosquito,” Aedes aegypti. Atmospheric chemistry α-Humulene is a biogenic volatile organic compound, emitted by numerous plants (see occurrence) with a relatively high potential for secondary organic aerosol formation in the atmosphere. It quickly reacts with ozone in sunlight (photooxidation) to form oxygenated products. α-Humulene has a very high reaction rate coefficient (1.17 × 10−14 cm3 molecule−1 s−1) compared to most monoterpenes. Since it contains three double bonds, first-, second- and third-generation products are possible that can each condense to form secondary organic aerosol. At typical tropospheric ozone mixing ratios of 30 ppb the lifetime of α-humulene is about 2 min, while the first- and second-generation products have average lifetimes of 1 h and 12.5 h, respectively. References Cycloalkenes Sesquiterpenes Humulus