4-Aminobutanoic acid lactam

Amino acids capable of forming lactams give low yields of (trifluoromethyl)amines. Thus, 4-aminobutanoic acid gives 4.4,4-trifluorobutylamine (14b) in only 7% yield, while 3,3,3-tri-fluoropropylaminc (14a) is formed from 3-aminopropanoic acid in 41 % yield.113... 

The commercially available lactam 76 is usable for amino acid synthesis as a chiral cyclic building block. 4-Fluoro- and 4,4-difluoro-3-aminocyclopentane carboxylic acids 79 and 81, potential inhibitors of y-aminobutanoic acid (GABA) aminotransferase, were synthesized as shown in Scheme 9.19 [39]. In this process, replacement of hydroxyl or carbonyl groups with fluorine was achieved by the use of DAST. Interestingly, the stereochemistry in substitution with DAST is retained [40], although it is by inversion in most cases [26]. Hydrolysis of 78 gave 80. 

Another important method for the preparation of amino acids involves direct cleavage of a cyclic ketone. In section 2.1.A, a lactam product (a cyclic amide) was produced from the ketone and then cleaved by hydrolysis, but in this section the ketone moiety is cleaved directly. A cyclic ketone such as cyclopentanone can be oxidatively cleaved with sulfuric acid. When this cleavage was followed by treatment with nitrosyl sulfate, an oximino acid 2.11) was formed. Catalytic hydrogenation of the oximino group gave 4-aminobutanoic acid (2.72). Similar treatment of cycloheptanone gave 6-aminohexanoic acid (2.75) and cyclononanone led to 8-aminooctanoic acid. ... 

Reaction of y-butyrolactones with ammonia is a convenient method for preparing ilve-membered ring lactams (2-pyrrolidinone derivatives). When 3-benzyl-7-butyro-lactone (2.23) was heated with ammonia, 4-benzyl-2-pyrrolidinone (2.24) was formed. 13 Hydrolysis led to 3-benzyl-4-aminobutanoic acid (2.25), an anti-spasmodic sedative.l3 Biologically active amino acids are discussed in chapter six. 

The hydrolysis of lactams is rather stndghtforward and most of the variety in this table results from different structural features and different synthetic manipulations of the lactams. Reaction I shows a simple hydroly of 3-methyl-2-pyrrolidinone 2.48) to give 2-ethyl-4-aminobutanoic acid 2.49). Several substituted derivatives were prepared, including 2-methyl-4-aminobutanoic acid, 3-ethyl-4 aminobutanoic acid, 3-propyl-4-aminobutanoic acid, 3-(l-methylethyl)-4-aminobutanoic acid, 2,3-diethyl-4-aminobutanoic acid, 2-ethyl-S-aminopentanoic acid, 3-methyl-5-amino-pentanoic acid, 3-ethyl-5-aminopentanoic acid, 3-propyl-5-aminopentanoic acid, and 3-( 1 -methylethyl)-5-aminopentanoic acid. l... 

The condensation reaction of an imine derived from an aldehyde with ethyl bromoacetate under Reformatsky53 conditions led to a mixture of amino-esters and P-lactams. When acetaldehyde was condensed with methylamine, Schiff base 4.116 was the product A Reformatsky reaction with ethyl bromoacetate gave a mixture of the P-lactam (4.117) and the amino-ester (4.118). Acid hydrolysis and hydrogenation led to the P-amino acid N-methyl-3-aminobutanoic acid (4.119). When benz-aldehyde was the aldehyde starting material, 3-(N-methylamino)-3-phenylpropanoic acid (4.120) was the final product. ... 

Specific enzymatic processes can introduce functionality in an enantioselective process. N-Benzyl-2-pyrrolidinone 5.164) was hydroxylated directly using an available enzymatic system, Beauveria sulfiirescens (ATCC 7159).72 The hydroxy-lactam (5.165) was then hydrolyzed and de-benzylated to give S-2-hydroxy-4-aminobutanoic acid, 5.25. 

Dissolution in neutral water gave ethyl 4-aminobutanoate.3 The iminium salt is much more reactive to ring opening than the lactam, giving the amino acid under very mild conditions. A number of lactams unsubstituted at nitrogen were converted to the iminium salt and were opened in neutral water to give the corresponding... 

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