2002 Fiscal Year Final Research Report Summary
New Preparations of Heterocydes Using Trimethylsilyldiazomethane
| Project/Area Number |
12672058
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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 |
Chemical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
AOYAMA Toyohiko Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (80080191)
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| Project Period (FY) |
2000 – 2002
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| Keywords | trimethylsilyldiazomethane / alkylidene carbene / vibsanol / 2-cyclopentenone / trichodenone C / aziridine / indole / azulene |
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| Research Abstract |
Synthesis of various heterocycles using trimethylsilyldiazomethane (TMSCHN_2), a stable and safe substitute for hazardous diazomethane, was investigated as follows.
1) Vibsanol, a benzofuran-type lignan isolated from the wood of Viburnum awabuki, was synthesized by the tandem cyclization of o-tert-butyldimethylsiloxyarylalkynes with excess paraformal dehyde in the presence of tetrabutylammonium fluoride as the key step.
2) Lithium salt of trimethylsilyldiazomethane (TMSC(Li)N_2), easily prepared from TMSCHN_2 with n-BuLi or LDA, smoothly reacted with γ-ketoaldehyde acetals to give 2-cyclopentenones via the 1,5-C-H insertion of alkyldene carbene in good yields. Using this method, the synthesis of trichodenone C, isolated from Trichoderma harzianum and exhibited cytotoxicity against cultured P388 cells, was accomplished.
3) TMSCHN_2 easily reacted with N-sulfonylaldimines to give selectively cis-N-sulfonylaziridines in high yields.
4) Reaction of TMSC(Li)N_2 with α-oxoketene dithioacetals gave thiophenes, homologous ketones, and homologous alkynes depending upon substrates used.
5) TMSC(Li)N_2 reacted with o-aminoacetophenones to give indoles via the N-H insertion of alkyldene carbene in good yields.
6) TMSC(Li)N_2 reacted with 4-aryl-2-oxobutanoic esters to give 2,3-dihydroazulenes via the alkyldene carbene intermediates which were easily converted to azulenes by oxidation with MnO_2 in good yields.
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