| Project/Area Number |
04403008
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
天然物有機化学
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
KUWAJIMA Isao Tokyo Institute of Technology, Faculty of Science, Professor, 理学部, 教授 (50016086)
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| Co-Investigator(Kenkyū-buntansha) |
HORIGUCHI Yoshiaki Tokyo Institute of Technology, Faculty of Science, Associate Professor, 理学部, 助教授 (80209296)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥30,900,000 (Direct Cost: ¥30,900,000)
Fiscal Year 1994: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥23,200,000 (Direct Cost: ¥23,200,000)
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| Keywords | Taxol. / Taxusin. / Stereoselective Hydroxylation. / Eight-Membered Ring Cyclization / タキソール / アトロプ異性 / 8員環閉環 / エンド規制 / タキシニン / タキサン骨格 |
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| Research Abstract |
We have designed a total synthesis of taxol as the optically pure form. Our strategy was highly dependent on the 8-membered B ring cyclization between dienol ethers and acetal, and it was realized at earlier stage by using model compounds containing aromatric C ring to produce the desired endo tricarbocycle with correct stereochemistry. Our next problem was how to make an optically pure alpha-hydroxyaldehyde as A ring fragment which may play important roles to control the enantioselectivity at each site. For such purpose, we developed a useful synthetic method of optically pure A ring fragment by employing Sharpless AD methodology to cyclohexanedione-aldehyde derivative. Further, a useful method for introduction of 7-OH group was also explored.
By combing these results, A fragment was connected with two types of C fragments such as cyclohexenone or anisol derivative, and then B ring cyclization was examined. The reaction took place nicely to give the desired tricarbocycles in good yields with correct stereochemistry. Stereoselective introduction of 7-OH group was readily performed by using our above methodology and we have succeeded to prepare two types of useful synthetic intermediates for taxol in optically pure forms. Both intermediates will be easily converted by applying the following transformation ; introduction of 1) C-8 methyl and 2) C-10 OAc group, 3) construction of D ring, and 4) acylation of C-13 hydroxy group.
Since most of them are already dissolved by us and others, it will be very promising to complete an efficient total synthesis of taxol in a near future.
It has also been proved our B ring cyclization methodology is very useful for the synthesis of taxusin and taxinine, and their synthetic studies will also complete in a short time.
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