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Data on the synthesis of chiral γ-lactams substituted at position 4 and the corresponding β-substituted γ-aminobutyric acids for the period from 1991 to 2006 are reviewed.Cyclic amides (lactams) are an often encountered structural element of medical products. The present review examines the preparation of γ-lactams (pyrrolidones) substituted at position 4. This group includes piracetam (oxiracetam, phenotropil, cebaracetam), rolipram, and others. The γ-amino acids corresponding to the above-mentioned lactams (analogs of the natural neuromediator γ-aminobutyric acid) also often exhibit biological characteristics, e.g., the β-aryl-substituted derivatives phenibut and baclofen. The 4-substituted lactams examined in this article and also the corresponding β-substituted γ-aminobutyric acids contain a chiral center* 2 . It is known that in most cases only the R-isomers of these compounds are biologically active, whereas the S-isomers are practically inactive. The production of optically pure isomers of these compounds therefore becomes an urgent issue. In this review methods of resolving racemic lactams into the optical isomers, various examples of asymmetric synthesis, and also enzymatic methods are examined.

A. Lebedev, L. Leite, M. Fleisher, and V. StonkusThe relative stabilita,, of 2-h.vdroxytetrahydrofi~ran and the tautomeric 4-hydroxybutanal was determined by the semi-empirical AM1 method. It was concluded that the cyclic tautomer predominates in the gas phase at 25~Vapor-phase dehydration of 2-hydro.wtetrahydrofitran in the presence o['porcelain and silica gel L leads to a quantitative yield o ['2,3-dihydrofuran.

1, 4-Butanediol is converted into tetrahydrofuran in the presence of silica gel at temperatures of 245-340~The mechanism of the conversion of I, 4-butanediol The dehydration-cyclization reaction of 1,4-butanediol is accelerated by catalytic amounts of mineral acids (HzSO 4, H3PO4), certain Lewis acids (PdCI2), and heterogeneous catalysts (silica gel, aluminosilicates, synthetic zeolites) [2][3][4]. Tetrahydrofuran is the main conversion product of 1,4-butanediol in the vapor phase at 245-340~ in the presence of silica gel and kieselguhr (Table 1). When using certain forms of silica gel as catalyst, the yield of tetrahydrofuran was 100%. In addition to tetrahydrofuran, the presence of 4-hydroxybutanal and 2,3-dihydrofuran has been established in the reaction products formed on dehydrogenation of 1,4-butanediol. As is known, the dehydration of alcohols characteristically uses the acid properties of the catalyst. From the results given in Table I, it follows that the surfaces of the silica gels investigated in this work differ significantly in the concentration of reactive acidic centers.Several possible reaction mechanisms for the cyclodehydration of diols have been discussed in the literature [4][5][6][7]. The suggestion has been made that Lewis acids form donor-acceptor bonds with the hydroxyl groups and induce synchronous elimination of water molecules and the cyclization reaction. According to another version, tetrahydrofuran is formed by the sequence of adsorption of diol onto Br6nsted acid centers, protonation by one of the hydroxyl groups, removal of a water molecule with the formation of a carbocation, and cyclization. Experimental data obtained for monoalkanols [8] are used as a basis for the suggestion regarding carbocation formation. Bartok and coworkers considered that the intramolecular cyclization of 1,4-butanediol occurs as a result of attack of a protonated OH group on a second hydroxyl group and belongs to the SN2 type of substitution reactions [5].Our investigations by quantum chemical methods showed that on full optimization of the geometry of the linear carbocation obtained by the dehydration of protonated 1,4-butanediol, it is possible to form an intermediate cyclic positively charged complex [7]. A similar complex was included in an empirical scheme for the mechanism when considering the conLatvian Institute of Organic Synthesis, Riga LV-1006.