1993 Fiscal Year Final Research Report Summary
Synthesis of Physiologically Active Compounds by Using Cyclization of Carbamoylmethyl Radicals
| Project/Area Number |
03671020
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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 | Kyoto pharmaceutical University |
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Principal Investigator |
IKEDA Masazumi Koto Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30028857)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIBASHI Hiroyuki Kyoto Pharmaceutical University Faculty of Pharmaceutical Sciences, Associate Pr, 薬学部, 助教授 (70028869)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Carbamoylmethyl Radical / Radical cyclization / Trachelanthamidine / Mesembranol / Elwesine / Pretazettine / beta-Lactam / ALkaloid |
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| Research Abstract |
We have found that the carbamoylmethyl radicals (=NCO-CH-) generated from alpha-cholroacetamides undergo cyclizations with intramolecular alkenes in regio- and stereo-selective manner to give a variety of lactams.
1. The N-allyl-alpha-chloroacetamides, upon tratment with Bu_3SnH and azoisobutyronitrile (AIBN) in refluxing benzene, gave fie-membered lactams. This reaction was applied for the synthesis of (-)-trachelanthamidine, a kainoid analog, ((〕SY.+-.〔))-mesembranol, and ((〕SY.+-.〔))-elwesine.
2. Similar treatment of omicron-alkenylphenyl-alpha, alpha-dichloroacetamides gave six- to eight-membered lactams in regioselective manner.
3. The N-vinylic alpha-haloacetamides also cyclized to give either four- or five-membered lactams, depending upon the substituents which can stabilize the adical intermediates formed after cyclizations. This cyclixation was applied for the synthesis of ((〕SY.+-.〔))-cotinine, a metabolite of nicotine, and beta-lactams such as (+)-PS-5 and (+)-thienamycin.
4. When N-allylic alpha-chloro-alpha-methelthioacetamides were heated with RuCl_2(PPh_3)_2 in benzene at 140ﾟC in a sealed tube, atom-transfer type cyclizations took place to give fic-membered rings. This cyclization was applied to the synthesis of (-)-trachlanthamidine and ((〕SY.+-.〔))-pretazettine.
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