2.5- Dichloro-3,6-diisobutylpyrazine

Dichloro-3,6-diisobutylpyrazine (237) is the starting material for a very similar synthesis of pulcherriminic acid (10).430 Pulcherri-minic acid, as already mentioned in Section I, is derived from pulcherrimin (9), a metabolite of the yeast Candida javlcherrima. The key step in the synthesis of pulcherriminic acid is the initial step of... 

Chloro-5-hydroxy-3,6-dimethylpyrazine with phosphoryl chloride gave a low yield of 2,5-dichloro-3,6-dimethylpyrazine (312) 3-chloro-5-hydroxy-2-methyl-pyrazine gave 3,5-dichloro-2-methylpyrazine (535) and 2-chloro-5-hydroxy-3,6-diisobutylpyrazine with phosphoryl chloride at 150° for 5 hours gave 2,5-dichloro-3,6-diisobutylpyrazine (101). 

An alternative approach applicable both to the synthesis of racemic aspergillic acid428 and neoaspergillic acid is illustrated by the synthesis (Scheme 50) of neoaspergillic acid (8).429 The initial reaction of dl-leucine anhydride (235) with phosphoryl chloride produces, in addition to the required monochloro compound (236), some dichloro compound (237), and flavacol (4). Reaction of the latter compound with a mixture of phosphoryl chloride and phosphorus pentachloride yields further 2-chloro-3,6-diisobutylpyrazine (236). The remaining steps of the synthesis involve reactions discussed previously in this review, with the exception that the hydroxamic function is protected by diazomethane methylation and finally regenerated by ethanolic hydriodic acid treatment.429... 

Chloro-2,S-dimethylpyrazine was not isolated from the reaction of DL-alanine anhydride with a mixture of phosphoryl chloride and phosphorus pentachloride, but the reaction gives a poor yield of (48, X = Q) and a small quantity of (48, X = OH). Gallagher et al. (282) found that DL-phenylglycine with phosphoryl chloride gave 2,5-dichloro-3,6-diphenylpyrazine and 3-hydroxy-2,5-diphenyl-pyrazine (presumably formed by loss of the elements of hydrogen chloride from an intermediate 2-chloro-5-hydroxy-3,6-diphenyldihydropyrazine) and Dunn et al. (95) from DL-leucine anhydride and phosphoryl chloride prepared flavacol, 3-hydroxy-2,5-diisobutylpyrazine, and a mature of chloropyrazines, whereas Ohta (101) used phosphoryl chloride and phosphorus pentachloride and obtained flavacol and a little 2[Pg.26]

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