Novel Tandem Desulfurization and Hydroxylation in Aqueous Media (Towards the Asymmetric Synthesis of New and Effective Anti-cancer Agents)
| Project/Area Number |
15550031
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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 | Shizuoka University |
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Principal Investigator |
YODA Hidemi Shizuoka University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (20201072)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | desulfurization / coupling reaction / hydroxylation / 1-electron transfer / sulfur-substituted lactam / Lewis acid / stereoselectivity / natural products synthesis |
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| Research Abstract |
Recent disclosures from this laboratory have demonstrated SmI_2-promoted tandem desulfurization and high erythro-selective coupling reactions of aromatic lactams with carbonyl compounds. Although significant progress, thus, has been made in advancing the versatility of sulfur-substituted lactams, the lack of studies concerning the reactivity toward simple Lewis acids is surprising except the lactol type of compounds. Herein we wish to report our successful efforts for the development of novel Lewis acid-mediated tandem reaction of phenylthio-substituted alicyclic and aromatic lactams in aqueous media, leading to the γ-hydroxylated products, whose process was further applied to the convenient total synthesis of isoindolobenzazepine natural product, chilenine.
Whereas the reactions with FeCl_3 and CuI gave the desired γ-hydroxylated product, but in low yield, respectively, use of CuCl or CuBr had a dramatic effect on the rate and smoothly brought about the taget compound in almost quantitative yields under these mild and readily available conditions. We were delighted to find that the same beneficial results were again obtained in reaction employing quaternary substituted phenylthiolactams containing aliphatic and aromatic alkyl side chains by replacement of the solvent system. We further found that the use of β-substituted and α,β-disubstituted γ-phenylthiolactams as well as the aromatic one underwent convenient reactions to afford the corresponding desulfurized hydroxylactams in quite high yields. In light of the above outcome, we turned our attention to the development of novel and convenient synthetic method of isoindolobenzazepine alkaloid, chilenine and accomplished the total synthesis of natural chilenine. This process will be widely applicable to the synthesis of other fused alkaloidal natural products such as new antitumor antibiotics, UCS 1025 series containing a quaternary hydroxyl group α to the nitrogen.
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Report
(3 results)
Research Products
(18 results)
