Reichstein process

Grafting a microbial oxidation of L-Srb into 2KLG on the Reichstein process, which is an obvious improvement to the latter, results in a two-stage fermentative process (Fig. 8.30a). China was the first country to develop [155] and universally adopt such a process [156]. Its production costs are said to be 30% lower that those of the traditional process [157]. Cerestar has claimed an 89% yield (100 g I.1 STY 78 g IT1 d ) of 2KLG from L-Srb in a mixed culture of G. oxy-dans and Bacillus thuringiensis [151]. Such processes have now been introduced in Europe, for example by KGS (Krefeld, Germany) and DSM (Dairy, Scotland). 

A fermentative or biocatalytic procedure for 2KLG calls for a completely different approach to the DSP of the latter and possibly also for the conversion of 2KLG into ASA. The basic problem is that 2KLG is dissolved in the culture supernatant as a salt, due to the necessity to titrate the culture with base to maintain neutrality. The conversion of 2KLG into ASA, in contrast, requires the free acid. Traditional solutions, such as spray-drying and acidification with sulfuric acid [170] and evaporative crystallization [171], are energy intensive and coproduce an equivalent of salt, which is, parenthetically, one of the objections against the Reichstein process. 

The survival of the Reichstein process has been prolonged further by a price-fixing cartel of the major producers of ASA, see Competition Commission, BASF AG and Takeda Chemical Industries Ltd a Report on the Acquisition by BASF AG of Certain Assets of Takeda Chemical Industries Ltd, London, 2001 [available from http //www.competi-tion-commission.org.uk]. 

Fig. 12.1 Reichstein process for vitamin C production. The D-glucose was hydrogenated to form D-sorbitol. The D-sorbitol was converted into L-sorbose by acetic bacteria. The L-sorbose was further oxidized with protection to form 2-KLG. The 2-KLG was then esterified and lactonized to form vitamin C...

The miCTobial transformation of D-sorbitol to L-sorbose is the most important industrial fermentation process of vitamin C in Reichstein process and two-step fermentation. Microorganisms are inhibited severely by high concentration of... 

Figure 16.2. Schematic of the Reichstein process for the technical synthesis of L-ascorbic acid.

Though the Reichstein process was applied for the industrial-scale production of l-AA for many years, the disadvantages of the process include low yield, high energy consumption, high amount of the organic solvent required, and serious environmental pollution. Therefore, many researchers have attempted to improve the performance of classical Reichstein process. 

The classical two-step fermentation process is the most successful process for l-AA production. During the two-step fermentation process, the final yield of L-sorbose on D-sorbitol is more than 99.5%, while the yield of 2-KLG on L-sorbose is more than 97%. Very few of the current industrial bioprocesses can achieve such yields. The whole classical two-step fermentation process yield is more than 90% of l-AA from glucose feed on the industrial scale, which is much higher than that of the Reichstein process. 

In 1928, the Hungarian biochemist Albert Szent-Gyorgyi isolated vitamin C, which was first designated as hexuronic acid, from the adrenal glands of animals and later from Hungarian paprika peppers. Between 1933 and 1934, the British chemists Sir Walter Norman Haworth and Sir Edmund Hirst and the Polish-Swiss chemist Tadeusz Reichstein succeeded in synthesizing vitamin C. The Reichstein process was adopted by F. Hoffmann-La Roche to produce vitamin C from 1934. The process includes one microbial oxidation step, from o-sorbitol to L-sorbose, and has been used commercially for about 80 years with many chemical and technical modifications to improve the efficiency of each step (Fig. 15.1). Currently more than 100,000 tons per year of pure vitamin C are produced worldwide. 

Fig. 15.1 The Reichstein process and microbial fermentation processes for L-ascorbic acid production. Three pathways for vitamin C production are shown The Reichstein process includes six chemical steps (Ca-Cf) and one microbial step (Ml). Ca catalytic hydrogenation, Cb protection of hydroxyl groups with acetone, Cc oxidation, Cd deprotection of acetone, Ce esterification with methanol, Cyiactonization. M2 microbial process includes three chemical steps (Ca, Ce, Cf) and three microbial steps shown as M2 in the figure. M3 microbial process includes one chemical step (Ca) and three microbial steps (shown as M3)...

In 1898, Gabriel Bertrand reported the formation of L-sorbose from D-sorbitol for the first time. In 1934, this reaction was adopted to produce vitamin C in the so-called Reichstein process (Reichstein and Griissner 1934) ... 

Once the Reichstein process was established, alternative processes for vitamin C production have been studied to produce 2KLGA, an intermediate of vitamin C production, mainly from three starting substrates via corresponding intermediates... 

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