Preparations of heterospirostanols and their pharmacological activities.
(3beta,20S,22S,25R)-22-Thiospirosol-5-en-3-ol (9) and (3beta,20S,22S,25R)-22-seleno-spirosol-5-en-3-ol (11) were prepared from diosgenin (3) via 26-iodopseudodiosgenin (6) as a key intermediate. Diosgenone (15), solasodinone (16), (20S,22S,25R)-22-thio-spirosol-4-en-3-one (17), (20S,22S,25R)-22-selenospirosol-4-en-3-one (18) and (20R,22S,25R)-spirosol-4-en-3-one (19) were prepared by Oppenauer oxidation of 3, solasodine 4, 9, 11 and (3beta,20R,22R,25R)-spirosol-5-en-3-ol 14, respectively. Oxidations of 15 and 16 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) provided corresponding dienone products, (20S,22S,25R)-spirosol-1,4-dien-3-one (20) and (20S,22S,25R)-22-thiospirosol-1,4-dien-3-one (21), respectively, while oxidation of 19 (C-20 diastereoisomer of 15) gave no dienone product but 21-exo vinyl product 22. 26-Thioacetylpseudodiosgenone (24) and 26-cyanoselenopseudodiosgenone (25) were prepared by treatment of 26-iodopseudodiosgenose (23), which was obtained by Oppenauer oxidation of 6, with potassium thioacetate and potassium selenocyanate, respectively. Compounds 15 and 19 exhibited more than 80% inhibitions in INF-gamma productions at 10.0 microM. Compounds 4 and 25 showed cytotoxic activities (IC(50) = 6 and 5 microM, respectively) against cancerous HCT 116 cell lines. Compounds 12 and 25 had antiurease activities (IC(50) = 12.4 and 11.4 microM, respectively), in which only the latter showed an inhibition zone (mean zone diameter = 12.2 mm) formed by Bacillus subtilis 168 trp.
Quan
Hang-Ji
HJ
College of Pharmacy, Yanbian University, Yanji, Jilin, 133000, People's Republic of China.
Koyanagi
Jyunichi
J
Ohmori
Koichi
K
Uesato
Shinichi
S
Tsuchido
Tetsuaki
T
Saito
Setsuo
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D013150:Spirostans / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014510:Urease / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013150:Spirostans; D007371:Interferon-gamma; D014510:Urease; D004144:Diosgenin