Anti-hepatitis B virus norbisabolane sesquiterpenoids from Phyllanthus acidus and the establishment of their absolute configurations using theoretical calculations.
Nineteen new highly oxygenated norbisabolane sesquiterpenoids, phyllanthacidoid acid methyl ester (1), and C-T (4-21), were isolated from Phyllanthus acidus Skeels, together with two known ones, phyllanthusols A (2) and B (3), whose sugar moiety was revised as glucosamine-N-acetate, rather than the previously assigned mannosamine-N-acetate. Compounds 2 and 3 were renamed respectively as phyllanthacidoids A (2) and B (3) to avoid confusion. All of the isolates except for 1 are glycosides, whose saccharide moieties possess a pentaoxy cyclohexane (scyllo quercitol) connecting with glucosamine-N-acetate or glucosyl moieties, which are first examples in natural products. Phyllanthacidoids N-R (15-19) with 8R configurations and/or 5,8-diketal skeleton, are unprecedented structures among norbisabolane sesquiterpenoids. Phyllanthacidoids S (20) and T (21) have the unusual tricyclo [3.1.1.1] oxygen bridge skeleton formed by a diketal system, of which the relative configurations of the aliphatic chain were assigned on the basis of heteronuclear coupling constants. The absolute configurations of compounds (1-21) were established by means of calculated electronic circular dichroism (ECD) and coupling constants. Compounds 1-5, 7-9, 10, and 14 displayed potential anti-hepatitis B virus (HBV) activities, with IC50 values of 0.8-36 μM against HBV surface antigen (HBsAg) and HBV excreted antigen (HBeAg), and the results indicated that the 5-ketal group and sugar moieties had contributions to the selectivity of HBsAg and HBeAg.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China.
Jun-Jiang
JJ
Lv
Shan
S
Yu
Ya-Feng
YF
Wang
Dong
D
Wang
Hong-Tao
HT
Zhu
Rong-Rong
RR
Cheng
Chong-Ren
CR
Yang
Min
M
Xu
Ying-Jun
YJ
Zhang
D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004187:Disaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000737:chemistry* / Q000276:immunology; D006515:Hepatitis B virus / Q000737:chemistry* / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D029803:Phyllanthus / Q000737:chemistry*; D011789:Quantum Theory; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism
D000998:Antiviral Agents; D001572:Benzofurans; D004187:Disaccharides; D006027:Glycosides; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012717:Sesquiterpenes; D013141:Spiro Compounds; C000593430:phyllanthacidoid A; C414101:phyllanthusol A; C414102:phyllanthusol B