Highly Functionalized Daphnane Diterpenoids from Trigonostemon thyrsoideum

Trigonothyrins A-C (1-3), which are highly functionalized daphnane diterpenoids, were isolated from the stems of Trigonostemon thyrsoideum. Compounds 1-3 represent the first examples of daphnanes with an oxygen-bridged four-membered-ring system, and a linkage mode of 12,13,14-orthoester. Compound 3 was observed to inhibit HIV-1 induced cytopathic effects. The EC50 value was 2.19 mu g/mL, and the therapeutic index (TI) was more than 90.

The authors thank two anonymous reviewers for their helpful suggestions and comments and also thank Ceiridwen Edwards for the comments on an early version of the manuscript. This work was funded by Fundacxao para a Ciencia e Tecnologia (FCT) project POCI/CVT/56758/2004. S. C., R. J. L., and P. T. are supported by FCT individual grants SFRH/BPD/26802/2006, SFRH/BPD/40786/2007, and SFRH/BD/42480/2007, respectively. G. L. was supported by the Portuguese-American Foundation for Development, Centro de Investigacxao em Biodiversidade e Recursos Geneticos, and University of Porto. F. G. and L. J. R. were funded by the grant CGL2005-03761/BOS. Y-P. Z. was supported by National Natural Science Foundation of China and Yunnan Province, China. Collection of samples in Afghanistan has been donewith the financial support of United StatesAgency for International Development. We also thank Tamal Mazumder, Debojit Saha, Chhotan Ghosh, andM. D. Eusuph for their support and help with sampling in India.