Phainanoids A–F, A New Class of Potent Immunosuppressive Triterpenoids with an Unprecedented Carbon Skeleton from Phyllanthus hainanensis

Phainanoids
A–F (1–6), six highly modified
triterpenoids with a new carbon skeleton by incorporating two unique
motifs of a 4,5- and a 5,5-spirocyclic systems, were isolated from Phyllanthus hainanensis. Their structures with absolute
configurations were determined by spectroscopic data, chemical methods,
and X-ray crystallography. Compounds 1–6 exhibited exceptionally potent immunosuppressive activities in vitro against the proliferation of T and B lymphocytes.
The most potent one, phainanoid F (6), showed activities
against the proliferation of T cells with IC50 value of
2.04 ± 0.01 nM (positive control CsA = 14.21 ± 0.01 nM)
and B cells with IC50 value of <1.60 ± 0.01 nM
(CsA = 352.87 ± 0.01 nM), which is about 7 and 221 times as active
as CsA, respectively. The structure–activity relationships
of 1–6 are discussed.