Shikimic acid configuration

Usami Y, Horibe Y, Takaoka I, Ichikawa H, Arimoto M (2006) First Total Synthesis of (-)-Pericosine A from (-)-Shikimic Acid Structure Revision and Determination of the Absolute Configuration of Antitumour Natural Product Pericosine A. Synlett 1598... 

The major adducts obtained in reactions of 32c with furan have been used to prepare both (+)-shikimic and (+)-5-epi-shikimic acids in their non-natural configurations, following the sequence depicted in Scheme 20 [49]. 

The prochiral center in citric acid is attached to two CH2COOH groups. The configurational question can, therefore, be phrased as the question, does acetyl-CoA contribute the pro-R or pro-S CH2COOH groups To provide an answer proved more difficult than for the relatively simple CabH2H cases so far discussed. The proof requires knowledge about several other enzymes and, as well, information about the chirality of compounds related to shikimic acid. 

The structural and configurational studies of quinic acid (1) by Fischer and Gerda Dangschat were extended during the Basle period to shikimic acid (2), the trihydroxycyclohexenecarboxyhc acid first isolated from the Chinese star anise by Eykman in 1885. This acid was first proved to be a... 

DHCHC starter unit. Unfortunately, this experiment did not allow the orientation of shikimic acid during incorporation into rap>amycin to be clearly determined. However, based on the stereochemical configuration of the rapamycin C4Z hydroxy and C43 methoxy substituents, it was suggested tbat C5 of sbikimate gives rise to C42 of rapamycin... 

The configuration of conduritol, and incidentally those of aZZo-inositol, mwco-inositol, and dihydroconduritol, was elucidated in 1939 by Dangschat and Fischer (6 ), who applied the acetonation-oxidation technique previously used so successfully on quinic and shikimic acids. The steps utilized were as follows ... 

The configuration of shikimic acid was established by H. 0. L. Fischer and G. Dangschat (85) through the series of reactions shown on p. 287. These steps leave no question regarding the configuration of shikimic acid and the position of the double bond. 

DAHP, 64) [135], an intermediate of the shikimic acid pathway, have been synthesized from corresponding aldehyde precursors. Several cychtols (e.g., 71-73) could be made from aldol products by radical or nucleophilic cyclization reactions [136-138]. An intermediate was also found to be a correctly configurated precursor to the spirocyclic Strep-tomyces metabolite sphydrofuran 69 [139]. In an approach resembling the inversion strategy an a-C-mannoside 68 has been prepared from D-ribose 5-phosphate [140]. 

The synthesis of 6a-carba-p-D-ffuctopyranose (165) (Scheme 26) comprised four key steps, namely the inversion of C4 configuration in quinic ester 160 to obtain 161, the shift of the ketal protection from C5-C6 to C4-C5 to provide 162, the stereocontrolled dihydroxylation of epi-shikimate 162, and the C6-deoxygenation reaction of advanced intermediate 164. Carbasugar 165 was obtained in an overall 12% yield from quinic acid 159 for a 13-step sequence. 

Oxidative interconversion of cyclitols and derivatives into acyclic, di-carboxylic acids has been widely used for structural elucidation in this series. Early applications of the procedure helped determination of the constitution of shikimic and quinic acids for example, cleavage of the 1,2,3-triol grouping of methyl dihydroshikimate (35) produced a dialdehyde (36), which was oxidized with bromine water to the (known) degradation end product, tricarballylic acid (37). This approach to structural problems has proved particularly successful for determining the configuration of glycosides and related compounds. 

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