2000 Fiscal Year Final Research Report Summary
Practical Synthesis of Polyamine Alkaloids Utilizing Chiral β-Lactams
| Project/Area Number |
11640542
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Organic chemistry
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
MATSUYAMA Haruo Graduate School of Science, Tokyo Metropolitan University, Associate Professor, 理学研究科, 助教授 (30087118)
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| Project Period (FY) |
1999 – 2000
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| Keywords | chiral β-lactam / polyamine alkaloids / cyclic imino ether / dihydroperiphylline / ring expansion / condensation and reduction |
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| Research Abstract |
Macrocyclic lactams containing a biogenetic base such as apermine and spermidine represent a new class of polyamine alkaloids which have a framework of β-amino acid and are of particular interest as synthetic targets in view of the broad biological activity, for instance as antibiotics and antihypertensives. (S)-dihydroperiphylline (1) is one of six alkaloids isolated from the leaves of Peripterygia marginata by Husson et al. All these alkaloids contain a 13-membered ring system derived from dicinnamoylspermidine. We recently reported the conjugate addition reaction of 6-and 5-membered cyclic hydrazines such as piperidazine and pyrazolidine to chiral vinyl sulfoxides and synthesized the chiral 9-and 8-membered lactams with high optical purity (up to 95% ee). The asymmetric syntheses of a 13-membered lactam alkaloid, celacinnine, and an 8-membered lactam alkaloid, homaline, were accomplished by this method. The present study provides a facile route to the synthesis of 13-membered alkaloid, (S)-dihydroperiphylline (1), starting from (S)-4-phenyl-2-azetidinone. A total synthesis of 1 involves a six-step sequence by successive ring expansions of smaller heterocyclic units. Our procedure permits clear-cut differentiation of the two secondary amino groups in the 13-membered lactam system by selective acylation in an early step. This method utilizes, as key steps, the condensation of (S)-4-phenyl-2-azetidinone with a 9-membered cyclic imino ether and following reductive ring-expansion of 4-oxotetrahydropyrimidine derivative. Both of these reaction process proceeded with retention of configuration around the chiral center to give an optical pure lactam. This is the first example of 13-membered lactam alkaloids using a chiral β-lactam as a chiral synthon, and this method can be applicable to the synthesis of other polyamine alkaloids containing a framework of β-amino acids.
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[Publications] M.Iyoda, K.Fuchigami, A.Kusaka, T.Yoshida, M.Yoshida, H.Matsuyama, and Y.Kuwatani: "Z-Tribenzo [c, g, k]-1, 2, 5, 6-tetradehydro [12] annulene, a Concave π-Electron System"Chem.Lett.. 860-861 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] M.Iyoda, N.Nakamura, M.Todaka, S.Ohtsu, K.Hara, Y.Kuwatani, M.Yoshida, H.Matsuyama, M.Sugita, H.Tachibana, and H.Inoue: "Novel Synthesis of Hexaaryl [3] radialenes via Dibromo [3] dendralenes"Tetrahedron Lett.. 41. 7059-7064 (2000)
Description
「研究成果報告書概要(欧文)」より
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