Synthesis of Thioloformate-Containing Lathyrane Diterpene Derivates via a [3,3] Sigmatropic Rearrangement and Their Anti-HIV Activity

The [3,3] sigmatropic rearrangement of a lathyrane diterpene with various allylic thionoformates was carried out, affording C17-thioloformate-containing lathyrane derivatives (<b>3a</b>-<b>3h</b>) for the first time. The reaction features a mild, rapid, and easy operation. All newly synthesized derivatives were evaluated for potential antiviral activity against HIV-1 and HIV-2. The incorporation of an appropriate thionoformate into the lathyrane diterpene framework enhances their anti-HIV activity. The derivative <b>3d</b>, featuring an <i>O</i>-(<i>p</i>-tolyl) carbonothionate substitution, exhibited the most potent anti-HIV activity, with an EC₅₀ value of 11.3 μM against HIV-1 NL 4.3 and an EC₅₀ value of 6.6 μM against HIV-2 ROD. Additionally, it demonstrated selectivity indices exceeding 4.0 and 6.8 against HIV-1 NL 4.3 and HIV-2 ROD, respectively.