229640-36-2Relevant academic research and scientific papers
Synthesis of the angiotensin converting enzyme inhibitor (-)-A58365A via an isomuenchnone cycloaddition reaction.
Straub,Padwa
, p. 83 - 85 (1999)
[formula: see text] The angiotensin converting enzyme inhibitor (-)-A58365A (1) was synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl-substituted isomuenchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo-phenylsulfonyl-substituted pyrrolidine imide. Treatment of the diazoimide with Rh2(OAc)4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative which was subsequently converted to the ACE inhibitor in six additional steps.
Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors of prolyl oligopeptidase (POP)
Haffner, Curt D.,Diaz, Caroline J.,Miller, Aaron B.,Reid, Robert A.,Madauss, Kevin P.,Hassell, Annie,Hanlon, Mary H.,Porter, David J.T.,Becherer, J. David,Carter, Luke H.
scheme or table, p. 4360 - 4363 (2009/04/06)
We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket.
An isomunchnone-based method for the synthesis of highly substituted 2(1H)-pyridones
Padwa, Albert,Sheehan, Scott M.,Straub, Christopher S.
, p. 8648 - 8659 (2007/10/03)
1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p- acetamidobenzenesulfonyl azide and triethylamine. Treatment of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (±)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh2(OAc)4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.
