HIV-1 Integrase Inhibitor, Dihydroobionin B, and the Investigation of Its Extraordinary Specific Rotation

Abstract

Dihydroobionin B (1), a chiral congenerof knownobionin B, was isolated from Pseudocoleophoma sp.KT4119, a freshwater fungus collected from a submerged wood blockin Kochi Prefecture, Japan, in 2020. The planar structure of 1 was characterized by mass and NMR spectral analysis andconfirmed by density functional theory (DFT)-based chemical shiftcalculations. Its absolute structure was determined by electroniccircular dichroism spectral analysis. Notably, 1 exhibitedan extraordinarily large specific rotation [[& alpha;](20) (D) +1080 (c 0.056, CHCl3)],which was verified by DFT-based specific rotation calculations. However,these calculations indicated that the sign of the specific rotationbased on static analysis was insufficient to determine the absoluteconfiguration in this case. Furthermore, Pseudocoleophoma KT4119 produced coleophomapyrones A (2) and B (3) and coleophomaldehyde A (4). While this isthe first report of 2 isolated from a natural source,it has also been prepared previously using a synthetic approach. Compound 1 potently inhibited HIV type 1 integrase (IC50 = 0.44 & mu;M) without significant cytotoxicity. Finally, dockingexperiments were conducted to propose a plausible mechanism for thebehavior of 1.