Gamma-lactams

A variety of cyclic products have been prepared from educts containing carbonyl as well as carboxylic groups. Thus, Hanusch-Kompa and Ugi prepared a large number of five-membered cyclic gamma-lactam compounds like 44 from levulinic acid. Other carbonylic acids can lead to compounds like 45, which is made from phthalaldehyde acid, valine methylester, and tert-butylisocyanide. The products like 46 and 47 can result from the U-4CR and further cyclization. 

Hanusch-Kompa C, Ugi I (1998) Multi-component reactions 13 synthesis of [gamma]-lactams as part of a multiring system via Ugi-4-centre-3-component reaction. Tetrahedron Lett 39(18) 2725-2728... 

The initial attempts were the synthesis of compounds represented earlier by structure A, where the ester function was built into proximity of the propanolamine. Even though shortened duration was achieved when a short-term infusion (40 min) was carried out, their duration tended to increase considerably after the administration of the infusion itself was prolonged (ca. 3 hours). A particularly novel spontaneous inactivation mechanism independent of enzyme activity was found to occur with compounds of structure A, where n was at least three (Eq. 10.1). This intramolecular cyclization reaction (which also occurs in vitro at neutral or basic pH), while not producing a carboxylate, does result in a predictably inactive tertiary amide product. In vivo testing of the gamma-lactam derivative did in fact show it to be inactive. 

Shu C, Liu MQ, Wang SS, Li L, Ye LW. Gold-catalyzed oxidative cyclization of chiral homopropargyl amides Synthesis of enantioenriched gamma-lactams. J Org Chem. 78(7) (2013) 3292-3299. 

V. Calvino-GasUda, R.M. Martin-Aranda, A.J. Lopez-Peinado, Alkatine carbons as effective catalysts for the microwave-assisted s)fnthesis of N-subsdtuted-gamma-lactams, Appl. Catal. A Gen. 398 (2011) 73-81. 

J. W. Kelly and J. T. Stewart, Separation of selected beta lactam antibiotic epimers on gamma cyclodextim ion exchange ethylvinyl benzene divinylbenzene copolymer and poly(styrene-divinyl benzene) copolymer stationary phases, J. Liquid Chromatogr., 14 2235(1991). 

Five-membered gamma- y-lactams and six-membered delta- 5-lactams can be prepared by heating appropriately substituted amino carboxylic acids to cause cyclization. 

---