| Co-Investigator(Kenkyū-buntansha) |
OHKURA Tamiko Keio Univ. Sch. of Med., Instr., 医学部, 助手 (20051740)
NAGASAWA Hideko Keio Univ. Sch. of Med., Instr., 医学部, 助手 (90207994)
KAWAMATA Takeshi Keio Univ. Sch. of Med., Assoc., Prof., 医学部, 専任講師 (80051530)
堀 均 慶応義塾大学, 医学部, 助手 (90119008)
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| Budget Amount *help |
¥42,700,000 (Direct Cost: ¥42,700,000)
Fiscal Year 1989: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1988: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1987: ¥36,000,000 (Direct Cost: ¥36,000,000)
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| Research Abstract |
Eudesmanolide type sesquiterpenes bearing alpha-methylene-gamma-lactone, such as pullchellin B, C, E and F, ivalin, asperin, ivasperin, alantolactone, telekin, tuberiferin, 1,2-dihydrotuberifern, artemisin, alloisosantonin and isosantonin, may be expected to exhibit antitumor activities. It is important for investigation of these biological activities that these optically active natural and non-natural products arc provided continuously. Instead of many conventional racemic sesquiterpenoids syntheses, we examined the synthesis of the optically active synthons by biological asymmetric reaction. The bicyclic compounds of 3,8-dioxo-4-methoxycarbonyl-9-methyl-, and 4,9-dimethyl-3,5-dioxo-DELTA^<4(10)>octalins which were expected as common key intermediates for the chiral syntheses of cudesmanolides, were both converted to the enantiomers in high chemical and optical yields by the selected yeasts. Since artemisin, isotelekin and tuberiferin have been synthesized as racematcs, the formal tot
… More
al syntheses of these natural products were achieved in terms of optically active compounds using the above mentioned chiral key intermediates. Non-natural type products and other eudesmanolides could also be easily synthesized. Accordingly, these active synthetics allow us to study more about biological/physiological activities and structure activity relationships.
Next we examined asymmetric hydrolyses of these acetoxy derivatives using 18 kinds of commercially available lipases in a relatively large scale. These 7-acetoxy derivative and 4-acetoxy-1-benzyloxy-2-methylcyclohexanone were easily converted to bicyclic compounds mentioned above. These compounds were subjected to asymmetric hydrolyses in high-optical and chemical yield. Furthermore, 2-methyl-2-propargyl-3-hydroxy-3-isopropenyl-cyclopentanone, which could be accessible as an optically active from by use of microbiological reduction, was converted to a common key intermediate for the syntheses of C_1-oxygenated ambrosanolides such as ambrosic acid and peruvin. Less
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