Yao-Yue Fan

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.

Mannolides A–C with an Intact Diterpenoid Skeleton Providing Insights on the Biosynthesis of Antitumor Cephalotaxus Troponoids

Three new diterpenoids, mannolides A-C (1-3), and two new Cephalotaxus troponoids, 4 and 5, were isolated from Cephalotaxus mannii and structurally characterized by spectroscopic data and X-ray crystallography. The discovery of compounds 1-3 featuring a new intact carbon skeleton, proposed as cephalotane, sheds new light on the biogenesis of Cephalotaxus troponoids, a rare class of antitumor C19 norditerpenoids. Antitumor tests showed that the tropone motif is essential for the activity.

Cephalotanins A-D, Four Norditerpenoids Represent Three Highly Rigid Carbon Skeletons from Cephalotaxus sinensis.

Four polycyclic norditerpenoids, cephalotanins A-D (1-4) representing three unprecedented carbon skeletons with highly rigid ring systems, were isolated from Cephalotaxus sinensis and structurally characterized by a combination of various methods. Compounds 1 and 2 are new skeletal norditerpenoid trilactones, while 3 and 4 are two norditerpenoids featuring different new carbon skeletons. Biosynthetic pathways for 1-4 were proposed by involving diverse and very fascinating chemical events with the coexisting cephalotane troponoids as the precursors. Compound 1 exhibited good NF-κB inhibition with an IC50 value of 4.12±0.61 μΜ.

Phainanolide A, Highly Modified and Oxygenated Triterpenoid from Phyllanthus hainanensis

Phainanolide A (1), a highly modified triterpenoid incorporating an unprecedented 6/9/6 heterotricyclic system and a highly oxygenated 5,5-spirocyclic ketal lactone, along with three new triterpenoids 2-4 were isolated from Phyllanthus hainanensis. Their structures were completely elucidated by a combination of diverse methods including 2D NMR, quantum chemical NMR and ECD calculations, and NMR data analogy with model compounds. Compounds 1-4 exhibited both remarkable cytotoxic and immunosuppressive activities.

Cascarinoids A–C, a Class of Diterpenoid Alkaloids with Unpredicted Conformations from Croton cascarilloides

Cascarinoids A-C (1-3), a new class of diterpenoid alkaloids with unpredicted conformations, were isolated and structurally characterized from Croton cascarilloides. It was demonstrated that the dispersion interaction might be one of the main contributors that stabilized the folded conformations for compounds 1-3. Compounds 2 and 3 showed moderate immunosuppressive activity against T and/or B lymphocyte cells.

Diterpenoids and Lignans from Cephalotaxus fortunei

Five new diterpenoids including two Cephalotaxus troponoids (1 and 2), two 17-nor-cephalotane-type diterpenoids (3 and 4), and an abietane-type diterpenoid (5), two new lignans (6 and 7), and a new trisnorneoligan (8) along with eight known compounds were identified from the twigs and leaves of Cephalotaxus fortunei. The structure of 11-hydroxyhainanolidol was revised as 10-hydroxyhainanolidol (9) by X-ray crystallographic data. Compounds 3 and 4 are the first examples of 17-nor-cephalotane-type diterpenoids that are likely the biosynthesis precursors of the co-occurring troponoids (e.g., 1, 2, and 9). Compound 1 exhibited cytotoxic activities against HL-60 and A-549 cells with IC50 values of 0.77 ± 0.05 and 1.129 ± 0.057 μM, respectively.

Hedyorienoids A and B, Two Sesquiterpenoid Dimers Featuring Different Polycyclic Skeletons from Hedyosmum orientale

Hedyorienoids A (1) and B (2), two sesquiterpenoid dimers, were isolated and characterized from Hedyosmum orientale. Compound 1 was an unprecedented heterodimer of two different classes of sesquiterpenoids furnished by forming an unusual 1,3-dioxolane ring, while compound 2 possessed a new dimerization pattern of two guaiane-type sesquiterpenoids. Biosynthetic pathways for 1 and 2 were proposed with the coexisting monomers chloranthalactone A (3) and hedyosumin A (4) as the precursors. Compounds 2 and 3 showed significant NF-κB inhibitory activity.

Mangelonoids A and B, Two Pairs of Macrocyclic Diterpenoid Enantiomers from Croton mangelong

(+)- and (-)-Mangelonoids A and B, two pairs of novel macrocyclic diterpenoid enantiomers featuring an unprecedented bicyclo[9.3.1]pentadecane core and a rare bridgehead double bond, were isolated from Croton mangelong. Their structures were unambiguously established using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. A plausible biosynthesis pathway for these compounds was proposed. (-)-Mangelonoid A exhibited NF-κB inhibition with an IC50 value of 7.27 ± 1.30 μM.

Six new diterpenoids from Croton laevigatus

Abstract Six new ent-labdane-type diterpeniods (1‒6), along with one known compound, were identified from the twigs and leaves of Croton laevigatus. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 2 and 7 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 4.11 and 8.33 μg/ml, respectively.

Cephanolides A–J, Cephalotane-Type Diterpenoids from Cephalotaxus sinensis

Ten new cephalotane-type diterpenoids, cephanolides A-J (1-10), and two known analogues were isolated and characterized from Cephalotaxus sinensis. Compounds 1-3 represent the first examples of A-ring-contracted cephalotane-type dinorditerpenoids, and compound 4 is an A-ring-contracted norditerpenoid. The biosynthetic pathways for compounds 1-4 are postulated with the coexisting cephalotane-type troponoids as the precursors. Compounds 11 and 12 showed significant cytotoxicities against a panel of tumor cell lines (A549, KB, HL-60, and HT-29) with IC50 values ranging from 0.464 to 6.093 μM.