Currently, due to the HIV latency mechanism, the search continues for effective drugs to combat this issue and provide a cure for AIDS. Gnidimacrin activates latent HIV-1 replication and inhibits HIV-1 infection at picomolar concentrations. This natural diterpene was able to markedly reduce the latent HIV-1 DNA level and the frequency of latently infected cells. Therefore, gnidimacrin is an excellent lead compound, and its anti-HIV potential merits further investigation. Twenty-nine modified gnidimacrin derivatives were synthesized and evaluated in assays for HIV replication and latency activation to establish which molecular structures must be maintained and which can tolerate changes that may be needed for better pharmacological properties. The results indicated that hydroxyl substituents at C-5 and C-20 are essential, while derivatives modified at 3-OH with aromatic esters retain anti-HIV replication and latent activation activities. The half-lives of the potent GM derivatives are over 20 h, which implies that they are stable in the plasm even though they contain ester linkages. The established structure–activity relationship should be useful in the development of gnidimacrin or structurally related compounds as clinical trial candidates.

The regioselectivity of the [3+2] cyclocondensation of trifluoromethyl-a,b-ynones with hydrazines can be readily tuned to preferentially afford either 3-or 5-trifluoromethylpyrazoles through variation of the reaction conditions. Under catalysis with copper(II) acetate (2.0 mol%), cyclocondensation proceeded smoothly to yield 3-trifluoromethylpyrazoles with high regioselectivity. In contrast, when the reaction was conducted in dimethyl sulfoxide under catalyst-free conditions, the formation of 5-trifluoromethylpyrazoles was predominantly observed.

The properties of C−F bonds, including high thermal and chemical stability, make derivatization of organic fluorine‐containing compounds by the activation of the C−F bond and subsequent functionalization quite challenging. We herein report a Lewis acid‐mediated defluorinative cycloaddition/aromatization cascade of 2,2‐difluoroethanols with nitriles as a novel synthetic method for the preparation of 2,4,5‐trisubstituted oxazoles. This reaction, which involves cleavage of two C−F bonds and the consecutive formation of C−O and C−N bonds in a one‐pot fashion, features a broad substrate scope and moderate to high reaction yields. Mechanistic studies revealed that the reaction is initiated by the Lewis acid‐mediated ring closure of the 2,2‐difluoroethanol to produce the fluoroepoxide intermediate.magnified image