The optically active (R)-6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine (1) is the amine moiety of a novel and potent
dopamine (D2 and D3) and 5-HT3 receptors antagonist AS-8112,
which is a clinical candidate expected to be a broad antiemetic
agent. Process development of an effective synthetic route to
the optically active amine 1 from N-Cbz- and N-Ts-l-serine
methyl esters was undertaken. In two potential scale-up
processes, the route from N-Ts-l-serine methyl ester (21) was
chosen because of its better overall yield (>30% yield for seven
steps) and handling. The optically active amine 1 with high
purity (>99.5% ee) was prepared via the reaction of the key
intermediate N-Ts-aziridine 23 with EtNH2 and successive
LiAlH4 reduction without racemization. Moderate scale-up
synthesis of the amine 1 and AS-8112 by condensation of 1 and
5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid
is described.
The water extract from the bulbs of Crocosmia crocosmiiflora (Nicholson) N. E. Br. (Iridaceae) and its pass-through fraction obtained by gel-filtration chromtography showed strong antitumor activity against Ehrlich carcinoma ascites and solid in Jcl-ICR mice when administered intraperitoneally. Some chemical studies revealed that the active principles in this plant were saponins consisting of medicagenic acid and polygalacic acid as the major sapogenins, and glucose, xylose, arabinose, rhamnose, and fucose as the sugar moieties. Crocosmia crocosmiiflora (Nicholson) N.E.Br.
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