A new approach has been demonstrated for the asymmetric synthesis of a-amino acids from a-keto acids using chiral reagents which are regenerated by the synthesis. The chiral reagents used were the N-amino-2-hydroxymethylindolines (9-9 and (9-16. The synthesis, resolution, and assignment of absolute configuration for these reagents is described. The application of ( 9 -9 and (9-16 to the asymmetric synthesis of a-amino acids depends on their combination with a-keto acids to form chiral hydrazono lactones (see Chart IX). Reduction of the C=N unit in these lactones (23,24, and 25) affords the corresponding hydrazino lactones (29,30, and 31) which are transformed to a-amino acids by hydrogenolysis of the N-N linkage and ester hydrolysis. By this process o-alanine and D-butyrine have been synthesized from pyruvic acid and a-ketobutyric acid using the reagent ( 3 -9 in optical purities of 80 and 90%, respectively. As a result of these studies, a solid basis exists for the design of chiral indoline reagents of still greater eficiency in the asymmetric synthesis of a-amino acids.(13) For another asymmetric synthesis of aspartic acid (optical purity ca. 88 %), involving the addition OF a-methylbenzylamine to maleic acid followed by catalytic hydrogenolysis, see A. P. Terent'ev, R. A.

The preparation of a number of 1,4-benzodiazepines substituted in the 3 position is described. The rearrangement of 7-chloro-l,3-dihydro-5-phenyl-2H-l,4-benzodiazepin-2-one 4-oxide with diacetyl sulfide yields largely the 3-acetylthio compound. Amines, ethers, and sulfides were prepared through the chloro intermediate. A 3-carbethoxybenzodiazepine was prepared and converted into oxazepam. The pharmacological test data of new and previously published compounds are given.

No abstract

A series of tetrahydropyrrolo[1,2-a]quinoxalines and tetrahydropyrrolo[1,2-a]pyrido[3,2-a]pyrazines were synthesized and tested for their ability to relax K+-depolarized aortic smooth muscle and antihypertensive activity. It was shown that compounds producing the most relaxation of aortic smooth muscle (5-[2,6-dimethoxyphenyl)methyl]-1,2,3,3a-tetrahydropyrrolo[1,2-a] quinoxalin-4(5H)-one and 5-[(2,6-dimethoxyphenyl)methyl]-5,6,6a,7,8,9-hexahydropyrrolo[1,2- a] pyrazine, 10 and 19, respectively) demonstrated the least hypotensive activity. Those compounds that were the most effective hypotensive agents (6a,7,8,9-tetrahydro-5-(phenylmethyl)pyrido[3,2-a]pyrrolo[1,2-a]++ +pyrazin- 6(5H)-one and 6a,7,8,9-tetrahydro-5-(4-pyridinylmethyl)pyrido[3,2-e]pyrrolo [1,2-a]pyrazin-6(5H)-one, 12 and 13, respectively) displayed little vascular smooth muscle relaxant activity.

No abstract