The Reichstein process in chemistry is a combined chemical and microbial method for the production of ascorbic acid from D-glucose in five steps.[1] This process was devised by Nobel Prize winner Tadeusz Reichstein and his colleagues in 1933 while working in the laboratory of the ETH in Zürich.[chronology citation needed]
Reaction steps
editThe reaction steps are:
- hydrogenation of D-glucose to D-sorbitol, an organic reaction with nickel as a catalyst under high temperature and high pressure.
- Microbial oxidation or fermentation of sorbitol to L-sorbose with acetobacter[2] at pH 4-6 and 30 °C.
- protection of the 4 hydroxyl groups in sorbose by formation of the acetal with acetone and an acid to Diacetone-L-sorbose (2,3:4,6−Diisopropyliden−α−L−sorbose)
- Organic oxidation with potassium permanganate (to Diprogulic acid) followed by heating with water gives the 2-Keto-L-gulonic acid
- The final step is a ring-closing step or gamma lactonization with removal of water.[3]
- Intermediate 5 can also be prepared directly from 3 with oxygen and platinum
The microbial oxidation of sorbitol to sorbose is important because it provides the correct stereochemistry.
Importance
editThis process was patented and sold to Hoffmann-La Roche in 1934.[chronology citation needed] The first commercially sold vitamin C product was either Cebion from Merck or Redoxon from Hoffmann-La Roche.[citation needed]
Even today industrial methods for the production of ascorbic acid can be based on the Reichstein process. In modern methods however, sorbose is directly oxidized with a platinum catalyst (developed by Kurt Heyns (1908–2005) in 1942). This method avoids the use of protective groups. A side product with particular modification is 5-Keto-D-gluconic acid.[4]
A shorter biotechnological synthesis of ascorbic acid was announced in 1988 by Genencor International and Eastman Chemical. Glucose is converted to 2-keto-L-gulonic acid in two steps (via 2,4-diketo-L-gulonic acid intermediate) as compared to five steps in the traditional process.[5]
Though many organisms synthesize their own vitamin C, the steps can be different in plants and mammals. Smirnoff concluded that “..little is known about many of the enzymes involved in ascorbate biosynthesis or about the factors controlling flux through the pathways".[6] There is interest in finding alternatives to the Reichstein process. Experiments suggest that genetically modified bacteria might be commercially usable.[7]
References
edit- ^ Teles, J. Henrique; Hermans, Ive; Franz, Gerhard; Sheldon, Roger A. (2015). "Oxidation". Ullmann's Encyclopedia of Industrial Chemistry. pp. 1–103. doi:10.1002/14356007.a18_261.pub2. ISBN 978-3-527-30385-4.
- ^ Wittko Francke und Wolfgang Walter: Lehrbuch der Organischen Chemie. S. Hirzel Verlag Stuttgart; 24. überarb Auflage 2004, ISBN 3-7776-1221-9; S. 480
- ^ Reichstein, T. und Grüssner, A. (1934): Eine ergiebige Synthese der L-Ascorbinsäure (C-Vitamin), Helv. Chim. Acta 17, S. 311–328
- ^ Brönnimann, C.; et al. (1994). "Direct oxidation of L-sorbose to 2-Keto-L-gulonic acid with molecular oxygen on Platinum- and Palladium-based catalysts". J. Catal. 150 (1): 199–211. doi:10.1006/jcat.1994.1336.
- ^ Harold A. Wittcoff, Bryan G. Reuben, Jeffery S. Plotkin (2012). Industrial Organic Chemicals. John Wiley & Sons, Page 370
- ^ Smirnoff, Nicholas (2001). "L-ascorbic acid biosynthesis". Vitamins and Hormones. 61: 241–66. doi:10.1016/s0083-6729(01)61008-2. PMID 11153268.
- ^ Hancock, Robert D.; Viola, Roberto (2002). "Biotechnological approaches for L-ascorbic acid production". Trends in Biotechnology. 20 (7): 299–305. doi:10.1016/S0167-7799(02)01991-1. PMID 12062975.
Literature
edit- Boudrant, J (May 1990). "Microbial processes for ascorbic acid biosynthesis: a review". Enzyme Microb. Technol. 12: 322–9. PMID 1366548.
- Bremus, C; Herrmann, U; Bringer-Meyer, S; Sahm, H (June 2006). "The use of microorganisms in L-ascorbic acid production". J. Biotechnol. 124: 196–205. doi:10.1016/j.jbiotec.2006.01.010. PMID 16516325.
