Chapter 22, Problem 2LGP

Shikimic acid is a key biosynthetic intermediate in plants and microorganisms. In nature, shikimic acid is converted to chorismate, which is then converted to prephenate, ultimately leading to aromatic amino acids and other essential plant and microbial metabolites (see the Chapter 21 Learning Group problem). In the course of research on biosynthetic pathways involving shikimic acid, H. Floss (University of Washington) required shikimic acid labeled with ${}^{13}C$ to trace the destiny of the labeled carbon atoms in later biochemical transformations. To synthesize the labeled shikimic acid, Floss adapted a synthesis of optically active shikimic acid from D-mannose reported earlier by G. W. J. Fleet (Oxford University). This synthesis is a prime example of how natural sugars can be excellent chiral starting materials for the chemical synthesis of optically active target molecules. It is also an excellent example of classic reactions in carbohydrate chemistry. The Fleet–Floss synthesis of $D\text{-}(-)\text{-}\left[1,7{\text{-}}^{13}C\right]$ -shikimic acid (1) from D-mannose is shown in Scheme 1.

(a) Comment on the several transformations that occur between d-mannose and 2. What new functional groups are formed?

(b) What is accomplished in the steps from 2 to 3, 3 to 4, and 4 to 5?

(c) Deduce the structure of compound 9 (a reagent used to convert 5 to 6), knowing that it was a carbanion that displaced the trifluoromethanesulfonate (triflate) group of 5. Note that it was compound 9 that brought with it the required ${}^{13}C$ atoms for the final product.

SCHEME 1 The synthesis of $D\text{-}(-)\text{-}\left[1,7{\text{-}}^{13}C\right]$ -shikimic acid (1) by H. G. Floss, based on the route of Fleet et al. Conditions:

(a) acetone, HA;

(b) BnCl, NaH;

(c) HCl, aq. MeOH;

(d) $Nal{O}_4$;

(e) $NaB{H}_4$;

(f) ${\left(C{F}_{3}S{O}_2\right)}_{2}O$, pyridine;

(g) 9, NaH;

(h) $HCO{O}^{-}N{H}_4{}^{\text{+}}\text{, }Pd\text{/}C$;

(i) NaH;

(j) 60% aq. $C{F}_{3}COOH$.