Using a Bioactive Eremophila -Derived Serrulatane Scaffold to Generate a Unique Carbamate Library for Anti-infective Evaluations.

The known -derived diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid () was targeted for large-scale purification, as this bioactive plant compound has proven to be an attractive scaffold for semisynthetic studies and subsequent library generation. Compound was converted to a selectively protected trimethyl derivative, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester (), using simple and rapid methylation conditions. The resulting scaffold was reacted with a diverse series of commercially available isocyanates to generate an 11-membered carbamate-based library. The chemical structures of the 11 new semisynthetic analogues were fully characterized by spectroscopic and spectrometric analysis. All natural products and semisynthetic compounds were evaluated for their anthelmintic, antimalarial, and anti-HIV activities. Compound was shown to elicit the greatest antiplasmodial activity of all compounds tested, with IC values of 4.6 and 11.6 μM against 3D7 and Dd2, respectively. Compound showed the greatest inhibition of development to fourth-stage larvae (L4) and induction of a skinny () phenotype (67.5% of nematodes) at 50 μM. Compound , which inhibited 59.0% of HIV production at 100 μg/mL, was the carbamate analogue that displayed the best antiviral activity.