1990 Fiscal Year Final Research Report Summary
Asymmetric Construction of New Chiral Building Blocks and these Application to the Syntheses of Natural Products
| Project/Area Number |
01571146
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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 |
Chemical pharmacy
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| Research Institution | Toyama Medical and Pharmaceutical University Faculty of Pharmaceutical Sciences |
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Principal Investigator |
HIRAI Yoshiro Toyama Medical & Pharmaceutical Univ, Faculty of Pharmaceutical Sciences, associate, 薬学部, 助手 (70111747)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Chiral building block / Biologically active natural product / Asymmetric intramolecular Michael reaction / Sharpless aymmetric epoxidation / Piperidine / Pyrrolidine / Pyrrolidone / Carbapenem |
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| Research Abstract |
An asymmetric construction of a common building block for the synthesis of several biologically active natural products offer the powerful methods for the synthesis of the desired natural products. Then, I have done the design of common building blocks for several alkaloids and an asymmetric construction of these building blocks. Furthermore, the conversion of these chiral building blocks to several alkaloids was carried out as follows.
1) An asymmetric construction of a piperidine and a pyrrolidone and these application to the alkaloids synthesis Treatment of an acyclic compound with (R)-1-phenylethylamine in THF under the kinetic conditions gave the 3, 4-functionalized piperidine derivative in 90% ee (80% yield). When (S)-1-phenylethyamine was used, the its enantiomer was obtained in similar ee. Recrystallization of the piperidines hydrobromide increased the ee up to 98%. These optically active piperidine derivatives were converted stereoselectively to (-)-ajmalicine, (-)-tetrahydroーalstonine, and (+)-yohimbine. The 3, 4-functionalized pyrolidone derivative also was synshesized in about 60% ee (80% yield) by the same procedure as described above. This pyrrolidone is a versatile chiral building block for the synthesis of strychnine alkaloids.
2) An asymmetric construction of pyrrolidines via the Sharpless asymmetric epoxidation A3-Hydroxy-2-functionalized Pyrrolidine derivative was prepared in 90% ee by utilizing the Sharpless epoxidation of the intermediate allyl alcohol starting from propargyl alcohol. A 3-Hydroxyー2,5-functionalized pyrrolidine derivative also was prepared through the Sharpless asymmetric epoxidation, a preparation of oxazoline ring system, and an intramolecular palladium-assist amino cyclization. These optically active pyrrolidines obtained were versatile chiral building blocks for the syntheses of pyrrolizidine alkaloids and carbapenems.
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Research Products
(10 results)
