1990 Fiscal Year Final Research Report Summary
Preparation of Physalins Possessing High Antitumor Activity
| Project/Area Number |
01550666
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Synthetic chemistry
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| Research Institution | Nagoya Institute of Technology |
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Principal Investigator |
KAWAI Masao Nagoya Inst. Tech. Dept. Applied Chem. Professor, 工学部, 教授 (60161270)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Shuki Nagoya Inst. Tech. Dept. Applied Chem. Associate. Prof, 工学部, 助教授 (30115670)
BUTSUGAN Yasuo Nagoya Inst. Tech. Dept. Applied Chem. Professor, 工学部, 教授 (90024207)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Plant Constituents / Physalis Alkekengi / Steroid / Structure Determination / Physalin / Spectral Analysis / Antitumor Activitity / Structure-Activity Relationship |
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| Research Abstract |
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.
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Research Products
(4 results)
