|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1990 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1989 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Physalin N and physalin O were isolated from the extracts of epigeal part of Physalis alkekengi var. francheti (Japanese name : Hozuki). Based on ^1H and ^<13>C NMR spectral analysis physalin N was assumed to be 7alphaーhydroxy1 derivative of physalin B. Similarly, physalin O was assumed to be 25, 27-dihydro derivative of physalin A. Upon catalytic hydrogenation physalin O gave the expected 7-dehydroxyー2, 3, 5, 6, 25, 27-hexahydrophysalin A, and acidーcatalyzed dehydration of physalin O afforded 2, 7-didehydrophysalin M, the already known dehydration product of physalin L. Thus, the structure of physalin O has been established as (25S)-25, 27-dihydrophysalin A unequivocally. Another constituent, tentatively named physalin P, was also isolated and its ^<13>C NMR spectra indicated that physalin P did not possess usual physalin skeleton but the rearranged structure called neophysalin skeleton. NMR, UV, and CD spectral analyses and the chemical transformation to the known 4, 7-didehydroneophysalin B have established the structure of physalin P to be 5alpha-hydroxy-6, 7-didehydro-5, 6-dihydroneophysalin B.
Antitumor activities of physalins and their derivatives were tested against HeLa cells, and the following structure-activity relationships have been proposed : i) Conjugated cyclohexenone at ring A is very important to the activity. ii) alpha-Hydroxy and alpha-epoxy groups at ring A or B markedly decrease the activity. iii) beta-hydroxy and beta-epoxy groups at ring A increase or do not affect the activity. Importance of methylene oxide bridge C(14)-O-C(27) and double bond C(25)=C(27) and of physalin skeleton are not certain.
Molecular design and synthetic approach towards the preparation of highly active physalins based on the above structure-activity relationship are being undertaken.