Synthesis of methyl shikimate from methyl (1,3,4/2,5)-2,3,4,5-tetrahydroxycyclohexane-1-carboxylate

✍ Scribed by Seiichiro Ogawa; Yasuyuki Aoki; Tohei Takagaki

• Publisher: Elsevier Science
• Year: 1987
• Tongue: English
• Weight: 504 KB
• Volume: 164
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(87)80155-6

✦ Synopsis

Shikimic acid (~-1) was first isolated from the oriental plant Illicium religiosum (in Japanese, shikimi) in 1885 by Eijkma&. After nearly 50 years, thanks to the pioneering works of Fischer and Dangschat4 during the 1930's, the complete structure and absolute stereochemistry of this acid were established.

In the early 1950's, shikimic acid was shown to be a key biosynthetic intermediate in the conversion of carbohydrate into aromatic amino acids, and this discovery, stimulated renewed interest in the compound and related substances. As a result, extensive studies of the synthesis have been conducted5. The first total synthesis was accomplished by Smissman et aL6 and McCrindle et al.' by thermal elimination reactions of the acetyl derivatives of methyl 2,3,4,5tetrahydroxycyclohexane-1-carboxylate (DL-3), which was prepared from the adduct formed in the Diels-Alder reaction of (lE, 34-l ,4:diacetoxy-1,3-butadiene with methyl acrylate or acrylic acid. The proposal of McCrindle et aZ.' that has the (1,2,5/3,4)-configuration was contested by Smissman and collaborators6, but eventually confirmed by McCasland et al.' on the basis of 'H-n.m.r. spectral data.

Since methyl ~~-(1,3,4/2,5)-2,3,4,5-tetrahydroxycyclohexane-l-carboxylate (DL-~), the 1-epimer of DL-3, is now readily available from the Diels-Alder adduct of furan and acrylic acid, it became of interest to assess the suitability of this compound as a precursor of methyl shikimate. We describe here a total synthesis of methyl DL-and r.-shikimate by elimination reactions of the tosyl derivatives of the esters DL-and ~-6, respectively.

The precursor, DL-5, was prepared in good yield by a modified procedure. Thus, treatment of methyl ~~-(1,3/2)-2,3-di-O-acetyl-2,3-dihydroxy-4-cyclo-* Dedicated to the memory of Hermann 0. L. Fischer on the centenary of his 100th birth.