Abstract
Diphenyl phosphorazidate(DPPA) and diethyl phosphorocyanidate (DEPC) are highly versatile reagents for many synthetic reactions as summarized in chart I, II and III, respectively. We report here syntheses of α-nitroketones using DEPC and methyl oxazole-4-carboxyl-ates using DPPA, and its application to the synthesis of a 2,4-diaminosugar antibiotic, prumycin 3. (1) Synthesis of α-Nitroketones Aromatic α-nitroketones can be conveniently prepared from aromatic carboxylic acids and nitromethane by the action of DEPC in the presence of triethylamine in dimethylformamide solution. (2) Synthesis of Methyl Oxazole-4-carboxyltes Various carboxylic acids react with methyl isocyanoacetate by the action of DPPA in the presence of potassium carbonate containing a small quantity of water to give methyl oxazole-4-carboxylates in good yields. The reaction of t-butoxycarbonyl-L-phenylalanine under similar conditions gave the oxazole with 92% optical purity. (3) Synthesis of Prumycin The oxazole 14 prepared by the DPPA method was converted to the oxazole 16, which was once recrystallized to give the oxazole 16 with 100% optical purity. The oxazole 16 was treated with HCl-MeOH, NaHCO_3, and then NaBH_4 to give two erythro isomers 18 and 19. The major isomer 18 with the lyxo configuration was converted to the α-aminoaldehyde 26 with the arabino configuration in 5 steps. Acid hydrolysis of 26, followed by hydrogenolysis afforded prumycin 3.
