Preparations of heterospirostanols and their pharmacological activities

Abstract

(3β,20 S,22 S,25 R)-22-Thiospirosol-5-en-3-ol ( 9) and (3β,20 S,22 S,25 R)-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), (20 S,22 S,25 R)-22-thio-spirosol-4-en-3-one ( 17), (20 S,22 S,25 R)-22-selenospirosol-4-en-3-one ( 18) and (20 R,22 S,25 R)-spirosol-4-en-3-one ( 19) were prepared by Oppenauer oxidation of 3, solasodine 4, 9, 11 and (3β,20 R,22 R,25 R)-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, (20 S,22 S,25 R)-spirosol-1,4-dien-3-one ( 20) and (20 S,22 S,25 R)-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-γ productions at 10.0 μM. Compounds 4 and 25 showed cytotoxic activities (IC 50=6 and 5 μM, respectively) against cancerous HCT 116 cell lines. Compounds 12 and 25 had antiurease activities (IC 50=12.4 and 11.4 μM, respectively), in which only the latter showed an inhibition zone (mean zone diameter=12.2 mm) formed by Bacillus subtilis 168 trp.