Aminoshikimic acid

Letelyan azide-free synthesis of oseltamivir phosphate was reported, where the key intermediate is aminoshikimic add produced by a two-step microbial process Bacillus pumilus to generate kanosamine followed by engineered E. coli to give aminoshikimic acid (Scheme 8.20) [81-83]. 

Stereospecific syntheses of (-)-3-epi-, 3(/ )-fluoro- and 3(S)-fluoro-shikimic acids and 3(/ )-amino-4(/ ),5(/ )-dihydroxy-l-cyclohexene-l-carboxylic acid (3(7 )-aminoshikimic acid) which used a method for obtaining gram quantities of shikimic acid from the seeds of Illicium anistwn (star aniseed) have been described. 

Dehydroquinic acid and [l,6-14C]-D-shikimic acid methyl ester were not incorporated, indicating a very early branch from the shikimate pathway. The intermediacy of 4-amino-3,4-dideoxy-D-araf>ino-heptulosonic acid 7-phosphate (37) was proposed, consistent with later findings on the role of the variant aminoshikimate pathway [94]. 

Figure 11.6 The aminoshikimate pathway to 3-amino-5-hydroxybenzoic acid.

A highly specialized synthesis converted (-)-shikimic acid 7.169) to 7.170. Reaction with azide and catalytic hydrogenation gave 5-aminoshikimate 7.171, methyl 5-amino-3,4-dihydroxy-l-cyclohexene carboxylate) in 21% overall yield. Amino acid 7.171 is an inhibitor of EPSP synthetase, and can be used as an herbicide,... 

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