The Synthesis of 3-deoxy-d-arabino-heptulosonic Acid 7-phosphate.

The demonstration that enolpyruvate-P plus n-erythrose 4-phosphate is converted enzymically to shikimic acid led to the suggestion (1) that the first intermediate in this process was 3deoxy-n-or&in&heptulosonic acid ‘I-phosphate (Compound V, Pig. 1). It was postulated that the newly formed hydroxyl group on C-4 had the stereochemistry shown in Compound V since it would then correspond to that of C-3 of 5dehydroquinate, the end product of the expected C-2-C7’cyclization of 3-deoxyn-or&no-heptulosonic acid 7-phosphate. In order to con6rm the proposed structure of the intermediite (2) and to make it available for a study of its enzymic conversion to 5-dehydroquinate (3), it was decided to synthesize 3deoxy+ara&noheptulosonic acid 7-phosphate by the series of reactions shown in Fig. 1. Starting with 2-deoxy-n-or&&w-hexose (2deoxy-D-glucose), the cyanohydrin was prepared and hydrolyzed, and the methyl 3deoxy-n-glue&heptonate (I) was isolated. Tritylation and then benzoylation of Compound I gave. the tetra-O-benzoyl-70-trityl methyl ester (II). This compound was detritylated by catalytic hydrogenolysis and then ester&d with diphenylphosphorochloridate to yield Compound III, which was not isolated. Unmasking of the phosphate group by catalytic hydrogenolysis (the benzene rings were reduced in this process) and saponification of the cyclohexylcarboxylic and methyl ester groups afforded 3-deoxy-o-gluco-heptonic acid 7-phosphate (IV), which was isolated as a crystalline cyclohexylammonium salt. The latter was oxidized by a pyridine-vanadium pentoxide reagent, and the resulting 3-deoxy-n-orabGw-heptulosonic acid 7-phosphate (V) was purified by ion exchange chromatography and isolated as a noncrystalline barium salt. The hydroxyl group on C-2 of the methyl 3-deoxyheptonate (I) had the Dqtpero configuration, since oxidation of Compound I with periodate to 2-oxysuccinaldehydic acid, followed by oxidation of the latter with silver oxide, gave 3deoxy-nqlyeerotetraric (o-malic) acid. In the cyanohydrin synthesis from aldoses “the isomer which is more readily accessible is the one that carries its hydroxyls on carbon atoms 2 and 4 in tram relationship” (4). It would appear, therefore, that this rule may apply also to 2deoxyaldoses. In the aldonic acids it has been shown that the phenylhydrazides (5), amides (6), benzimidazoles (7), and alkali metal salts (8) are dextrorotatory if the hydroxyl group on C-2 is on the right, and vice versa. This relationship holds also for the