Isolation, Synthesis, and Structure–Activity Relationship Study on Daphnane and Tigliane Diterpenes as HIV Latency-Reversing Agents

Three
new diterpenes, stellejasmins A (1) and B (2) and 12-O-benzoylphorbol-13-heptanoate
(3), were isolated from the roots of Stellera
chamaejasme L. The structures of 1–3 were elucidated by extensive NMR and mass spectroscopic
analyses. Compounds 1 and 2 are the first
derivatives containing a hydroxy group at C-2 in the family of daphnane
and tigliane diterpenes. The presence of a chlorine atom in 1 is unique in the plant metabolite. Compound 3 has an odd-number acyl group, which is biosynthetically notable.
Human immunodeficiency virus (HIV) LTR-driven transcription activity
was tested with 1–3 and 17 known
diterpenes isolated from S. chamaejasme L. and Wikstroemia retusa A.Gray.
Among these, gnidimacrin (4), stelleralide A (5), and wikstroelide A (20) were highly potent, with
EC50 values of 0.14, 0.33, and 0.39 nM, respectively. The
structure–activity relationship (SAR) was investigated using
20 natural and eight synthetic diterpenes. This is the first SAR study
on natural daphnane and tigliane diterpenes.