Integrasone Derivatives Isolated from Lepteutypa sp. KT4162 and Their Anti-HIV-1 Integrase Activity.

Five integrasone derivatives, integrasone C ( 1 ), isointegrasone C ( 2 ), integrasone D1 ( 3 ), integrasone D2 ( 4 ), and integrasone E ( 5 ), were isolated from the culture broth of Lepteutypa sp. KT4162. Neither conventional NMR analyses nor DFT (density functional theory)-based computationally assisted chemical shift discussions were sufficient to elucidate the relative configuration of the 1,4-epoxydiol moiety. A combined analysis using the calculated ⁿ J _CH values and HMBC spectra was helpful to establish the relative configuration. The absolute configurations of 1 - 5 were determined using DFT-based ECD (electronic circular dichroism) spectral analysis. Biological assays of these compounds revealed that 2 potently inhibits HIV-1 integrase without cytotoxicity.