1997 Fiscal Year Final Research Report Summary
Development of novel hypervalent iodine reagents and their applications to stereoselective synthesis of biologically active natural products
| Project/Area Number |
08457584
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
KITA Yasuyuki Faculty of Pharmaceutical Sciences, Osaka University, Professor, 薬学部, 教授 (00028862)
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| Project Period (FY) |
1996 – 1997
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| Keywords | hypervalent iodine (III) reagents / quinone imine / phenolic coupling / sulfur-containing heterocyclic compounds / alpha-azidation / discorhabdins / makaluvamine F |
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| Research Abstract |
In this project, we focussed our attention on the development of novel reactions using hypervalent iodine (III) reagents activated by Lewis acids such as BF_3・Et_2O and TMSOTf, and their applications to the synthesis of biologically active natural products.
We recently reported the nucleophilic substitution of phenol ethers using phenyliodine (III) bis (trifluoroacetate) (PIFA). The reaction is efficient for the introduction of nitrogen, oxygen, carbon, and sulfur nucleophiles to phenol ethers. In this project, the applications of activated hypervalent iodine reagents to intramolecular cyclization reactions have been developed, which are described below.
i) The intramolecular cyclization of phenol ethers bearing an alkyl azide side chain directly gave quinone imine derivatives in good yields using PIFA-TMSOTf. This reaction was also found to be effective for the synthesis of indoloquinone-imines, key precursor to marine anti-tumor alkaloids.
ii) The intramolecular phenolic coupling reaction using PIFA-BF_3・Et_2O enabled to synthesize the essential structure of amaryllidaceae alkaloids and multi-functionalized biaryl compounds in good yields.
iii) A novel and efficient synthesis of sulfur-containing heterocyclic compounds using PIFA-BF_3・Et_2O from phenol ethers bearing benzylthioalkyl side chain was developed.
Furthermore, we found a novel method for alpha-azidation of cyclic sulfides. The combination of Phl=O and TMSN_3 allowed alpha-azidation of dihydrobenzothiophen derivatives, which are easily aromatized and labile under oxidative conditions, in moderate yields. These findings will provide powerful tools for the total synthesis of sulfur-containing discorhabdins.
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