Production of Psicose by Chemical Epimerization of Fructose
Before any biological attempt, we tried to synthesize the rare sugar Psicose by chemical epimerization. This epimerization only works with ketose sugars. We have identified one sugar that can be used in the synthesis, D-Fructose, which is an epimere in C3 of D-Psicose. This sugar is abundant and cheap. It is found in honey, tree and vine fruits, flowers, berries, and most root vegetables. Fructose and Psicose exist naturally in 5 forms (anomers) (Figure 1).
After researching publications we found some that described the epimerization process (Figure 2) but nothing about chemical production and we decided to try the conditions described by Doner .
In this publication, the authors screened some bases to find the best experimental procedure (Table1).
We applied the conditions described in the literature  for the epimersation of D-Fructose into D-Psicose:
- The first condition: with a Triethylamine like base, D-Fructose (5.00 g) was stirred in both 5% aqueous and methanolic triethylamine (20 mL) at 60°C for 18 h and evaporated to a syrup. The crude product was analyzed by NMR spectroscopy 360 MHz in D2O.
- The second condition: with a Pyridine like base, after early recognition that this is the most effective and convenient base, it was examined under various reaction-conditions. The same isolation procedure was used, regardless of the experiment. At the completion of a given reaction, pyridine was removed from the concentration with the aid of toluene.
We decided firstly to take the NMR spectra of Mannose, Glucose, Fructose and Psicose to have some references. The results are presented in Figures 3 to 7.
The NMR spectrum showed characteristic peaks for each of the sugars (Table 2). They will be necessary to analyze the NMR spectrum of the crude product of our synthesis experiments.
|δ1 (ppm)||δ2 (ppm)||δ3 (ppm)||δ4 (ppm)|
After reactions in the above described conditions and analysis by NMR (Figure 8) we observed the formation of Psicose, in trace amounts, and also the production another sugar similar to Glucose and Mannose. We were unable to estimate the quantity of Psicose in our batch because its peak is overlapped by other peaks.
D-Psicose can be produced by chemical epimerization of D-Fructose in trace amounts that cannot be correctly estimated by RMN analysis because many characteristic peaks of different sugar are superimposed.
Our conclusion mets the one of Doner : the bio-production is the solution to synthesize Psicose.
-  Doner WL. Isomerization of d-fructose by base: Liquid-chromatographic evaluation and the isolation of d-psicose. Carbohydrate Res (1979) 70, 209-216.
Karen Becherel1, Dr. Aurélien Alix2, Dr. Geneviève Estenne-Bouhtou1, Dr. Pierre Alexandre Driguez1, Eric Nicolaï1, Dr. Alain Fournier1 and Prof. David Bonnaffé2
- 1 Sanofi-Aventis SA 2 Institute of Molecular Chemistry and Materials of Orsay (ICMMO), Univ. Paris-Sud, University Paris-Saclay