Synthesis of 2,6-Bridged Piperazine-3-ones by N-Acyliminium Ion Chemistry
- 1 May 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 68 (11) , 4486-4494
- https://doi.org/10.1021/jo0342572
Abstract
Several 2-substituted and 2,5-disubstituted piperazine-3,6-diones were synthesized starting from readily available alpha-amino acids. After activation of a lactam carbonyl via introduction of a methoxycarbonyl group onto nitrogen, this carbonyl was selectively reduced. Treatment of the resulting urethane with protic acid generated the corresponding N-acyliminium ion, which was trapped by a nucleophilic C2-side chain to provide 2,6-bridged piperazine-3-ones. Several aromatic, heteroaromatic, and nonaromatic side chains were used as pi-nucleophiles. In addition, the effect of the presence of a C5-methyl group on the stereochemical outcome of the cyclization was examined.Keywords
This publication has 23 references indexed in Scilit:
- Pharmacokinetic–pharmacodynamic modelling of the hypothermic and corticosterone effects of the 5-HT1A receptor agonist flesinoxanEuropean Journal of Pharmacology, 2002
- Pulse Pressure Changes With Six Classes of Antihypertensive Agents in a Randomized, Controlled TrialHypertension, 2001
- Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-IBioorganic & Medicinal Chemistry Letters, 2001
- A New, More Efficient, and Effective Process for the Synthesis of a Key Pentacyclic Intermediate for Production of Ecteinascidin and Phthalascidin Antitumor AgentsOrganic Letters, 2000
- A Practical Synthesis of the ABC Ring Model of Ecteinascidins.CHEMICAL & PHARMACEUTICAL BULLETIN, 2000
- Enantioselective Total Synthesis of Ecteinascidin 743Journal of the American Chemical Society, 1996
- Eltoprazine, a drug which reduces aggressive behaviour, binds selectively to 5-HT1 receptor sites in the rat brain: an autoradiographic studyEuropean Journal of Pharmacology, 1990
- Stereocontrolled total synthesis of (.+-.)-quinocarcinJournal of the American Chemical Society, 1988
- Synthetic approach to quinocarcinTetrahedron Letters, 1987
- A Promising Cyclization of the 3-Arylidene-6-arylmethyl-2,5-piperazinedione to Construct Tricyclic Lactam as an Intermediate to Saframycin SynthesisHETEROCYCLES, 1987