Jyunichi Koyanagi

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.

Cytotoxic Activity toward KB Cells of 2-Substituted Naphtho[2,3-b]furan-4,9-diones and Their Related Compounds

We investigated the cytotoxic activity of 2-substituted naphtho[2,3-b]furan-4,9-diones. We have previously synthesized 33 types of 2-substituted and related compounds, and the cytotoxic activity of these compounds was then examined by a KB cell culture assay. 2-(3-Furanoyl)benzoic acids and 1,4-naphthoquinones had no activity. 2-Acetyl-4,9-dimethoxynaphtho[2,3-b]furan 4 showed low activity. However, parent naphtho[2,3-b]furan-4,9-dione 2 and most 2-substituted derivatives exhibited cytotoxic activity. The parent structure was therefore for cytotoxicity. 2-Formylnaphtho[2,3-b]furan-4,9-dione 11 had particularly potent activity (ED50=0.09 μg/ml).