Formaldehyde formose from

So far, a number of ways have been proposed for the chemical synthesis of carbohydrates, employing the following as substrates 1, acetylenes 2, alkenes 3, dihydropyrans 4, cyclitols 5, dienes and 6, amino acids. All of these processes, however, require eomplicated synthetic procedures of 5 to 10 (or more) steps for the complete synthesis of monosaccharides, and the final yields of diserete carbohydrates are very low. In contrast, the synthesis of formose from formaldehyde proceeds directly with a high yield this could constitute a promising, economical supply of carbohydrates on an industrial scale. 

Arthur L. Weber (1998), now working at the Seti Institute of the Ames Research Center at Moffett Field, reports the successful synthesis of amino acid thioesters from formose substrates (formaldehyde and glycolaldehyde) and ammonia synthesis of alanine and homoserine was possible when thiol catalysts were added to the reaction mixture. On the basis of his experimental results, Weber (1998) suggests the process shown in Fig. 7.10 to be a general prebiotic route to amino acid thioesters. 

The formation of sugars from the reaction of formaldehyde under alkaline conditions was discovered in 1861 and is known as the formose reaction , although it is not understood fully (Figure 8.7). It requires the presence of suitable inorganic catalysts such as Ca(OH)2 or CaCOr, either of which may be found on a prebiotic Earth. The reaction is autocatalytic and produces over 40 different types of sugars, some rings, some long chains. 

Figure 7.4 Schemae of the formose reaction (a) spontaneous, slow formation of glycolaldehyde from formaldehyde (b) after one cycle, one new molecule of glycolaldehyde is produced. The structural isomers of sugars are specified by the carbon skeleton and by the position of the carbonyl group (open circle). (Adapted, with some modifications, from Maynard Smith and SzathmSry, 1995.)...

Weber AL. Prebiotic amino acid thioester synthesis thiol-dependent amino acid synthesis from formose substrates (formaldehyde and glycolaldehyde) and ammonia. Orig. Life Evol. Biosph. 1998 28 259-270. 

From Formaldehyde.—Historically and physiologically, the most important synthesis of hexose mono-saccharoses is from formaldehyde. In 1861 Butlerow found that dioxymethylene (tri-oxymethylene), produced by polymerizing formaldehyde, yielded with hot lime water a sweet substance to which he gave the name of methylenitan. The substance reduced Fehling s solution, but was optically inactive and non-fermentable with yeast zymase. Later, Loew obtained a sweet, non-fermentable syrup by the direct action of lime-water on formaldehyde. This substance he called formose. He afterward obtained what he considered another sugar by the action of magnesium hydroxide upon formaldehyde. This substance was fermentable by yeast and to it he gave the name of methose. In 1887, Fischer and Tafel... 

The formation of monosaccharides from formaldehyde was first described by Butlerow in 1861. He isolated a product, a sweet compound having an elemental analysis corresponding to that calculated for C7H14O6, from a formaldehyde solution containing calcium hydroxide, and named it Methylenitan. The term Formose was first given by... 

The formose reaction is principally an aldol reaction (anionic mechanism) of formaldehyde in an aqueous solution. By a complex repetition of the reaction, the carbon chain grows, to yield a variety of monosaccharides from C2 to Cs. 

In order to eliminate Cannizzaro effects from the data for the formaldehyde reaction-rate, the formose reaction-rate, Tf was defined [total... 

The Cannizzaro reaction of formaldehyde is far from a simple kinetic process that could be characterized by first- or second-order kinetics, and that would be a single reaction in which methanol and formate are produced. Rather, it proceeds in alkaline medium in conjunction with the formose reaction, the autocatalytic self-addition of formaldehyde to produce glycolaldehyde, which is then followed by aldol reaction to afford higher aldoses and ketoses. Mono-, di-, tri-, and tetra-valent bases, as well as nitrogenous bases, have been reported to catalyze both reactions homo-... 

The formaldehyde conversion-level has a definite effect on the product distribution. Most evident is the fact that the product obtained at complete conversion is markedly different from that obtained at intermediate conversion levels. Figure 16 shows the distribution, by number of carbon atoms, of the C3 and higher species produced in the formose reaction at 60° as a function of conversion of formaldehyde. Weight percents are regarded as identical to area percents of the gas-liquid chromatograms of the reduced sugars. No direct dependence on formaldehyde feed-rate is apparent. Three- and four-carbon compounds preponderate at low conversion levels at complete conversion, the terminal products are C4, 10% Cr 30% Co, 55% and C, 5%. 

Besides nucleobases, the primeval RNA-like polymers may have contained ribose and phosphate entities. Ribose may have been abundant as one of the products of the autocatalytic formose reaction, which was discovered by Butlerov in 1861 [304] and which yields a mixture of pentoses and hexoses from formaldehyde. Although Butlerovs reaction remains the only known autocatalytic reaction that does not require specific catalysts, the importance of this reaction for prebio-logical syntheses has been questioned since the yield of ribose in the product mixture is usually low. Recent studies have shown, however, that the yield of ribose can be selectively enhanced by the presence of phosphate in the reaction medium [305], by UV illumination [16], and by conducting the reaction in the presence of catalytic mineral templates [306]. More recently, it has been demonstrated that the yields of pentoses increase to 60% and those of the ribose proper rise to 20% in the presence of a zinc-proline complex as a catalyst [15]. The Zn world settings may have favoured autocatalytic ribose formation from photosynthesized substrates by providing mineral templates, UV irradiation, and plenty of Zn2-t ions as catalysts. 

The formation of methylenitan from hot lime water and what was really formaldehyde by Butlerow (1861) (see p. 548) was regarded by him as the first synthesis of a sugar, and after Hofmann (1868) had shown that Butlerow s dioxymethylene was formaldehyde (see p. 443), Loew, using a 4 per cent solution of this and cold lime water, obtained a syrup containing CgHigOe, with reducing properties, which he called formose . It underwent lactic but not alcoholic fermentation. By a modified process Loew obtained from formaldehyde what he called methose , which underwent alcoholic fermentation. These were later shown to be mixtures. ... 

A review in Russian on the synthesis of carbohydrates from formaldehyde has appeared. An investigation of the formose reaction by g.c.-n.m.r. has shown that intermediate glycoaldehyde, glyceraldehyde, and dihydroxyacetone are present as mixtures of monomers, e.g. hydroxy carbonyl compounds, epoxides and hydrates, and dimers such as half and full acetals. Further study of the barium chloride-catalysed formose reaction at pH 12 has shown that the main product forming 33% of the total sugars is the branched pentulose (1). The sugar yield reached a constant value at 70% completion of the reaction, i.e., within... 

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