Arabinose phenylhydrazone

A strategy has been described for the synthesis of 2-ethyIthio-6-(3-hydroxy-1,2-0-isopropylidenepropyl)pteridin-4(3//)-one 90 which can be used as a useful intermediate for the conversion of neopterin to biopterin. Diaminopyrimidinone 86 reacts with D-arabinose phenylhydrazone 87, the obtained diastereomeric mixture 88 is converted into its isopropylidene derivative 89 which under oxidation conditions yields 90 <00H(53)1551>. 

The condensation of 2,4,5-triamino-6-hydroxypyrimidine and 5-deoxy-L-arabinose phenylhydrazone 1042, followed by oxidation of the intermediate 1043, gave biopterin 1044. The tetrahydrobiopterin is the natural cofactor of phenylalanine hydrolase. Various stereochemical isomers were also pre-... 

L-Arabinose Phenylhydrazone. This was prepared by the procedure of Chavanne (59) mp 152°-153°C. 

The condensation of 2,5,6-triamino-4(3//)-pyrimidone with L-arabinose-phenylhydrazone leads to analogous tricyclic adducts which are, however, more sensitive to oxidation and more difficult to handle. The same type of adducts have also been observed during the condensation of 5,6-diamino-2-methyl-4(3//)pyrimidone with the phenylhydrazones of D-arabinose (e.g., (346)) or 5-deoxy-L-arabinose (e.g., (347)) (Scheme 56) <89MI 718-05). The various hydrofuro- and hydropyrano[3,2- ]pteridine derivatives are expectedly valuable intermediates for the synthesis of 6-substituted pteridines which were obtained by air oxidation in alkaline medium or more directly by treatment with p-benzoquinone <90MI 718-08) and iodine/H202, respectively (348) and (349) (Scheme 56). 

More information about the mechanism of the Viscontini reaction has been collected from model studies condensing 4,5,6-triamino-2-methylthiopyrimidine (338) in a similar manner with the phenylhydrazones of l- (339) and D-arabinose and omitting the iodine oxidation step (Scheme 55). Under these conditions an interesting intermediate, consisting of a tricyclic pteridine ring system (341), was formed by intramolecular adduct formation of the trihydroxypropyl sidechain on to the 7-position of the 5,6-hydropteridine precursor (340) (Scheme 55). The main reaction product could be crystallized and the structure unambiguously proven by an x-ray analysis <90HCA808). 

The H NMR spectra of the pyrano[3,2-< ]pteridine (341) and its enantiomer derived from the phenylhydrazone of D-arabinose (343) show a time-dependent change due to the formation of an equilibrium involving the isomeric furo[3,2- ]-pteridines. Analogous results were obtained with 5,6-diamino-3-methyl-2-methylthio- and 5,6-diamino-2-methylthio-4(3//)-pyrimidone (342), respectively, leading in the latter case even to a separation of the two enantiomers (344) and (345) with respect to the chiral centers at the 6- and 7-position of the pteridine moiety (Equation (15)). 

The similar polarographic behavior of semicarbazones, hydrazones, phenylhydrazones, and oximes of D-glucose, D-galactose, and n-mannose was described in another paper. For the aldoses studied, the equilibrium and rate constants for the formation of their oximes, semicarbazones, and hydrazones were determined at several different pH values, and it was found that their reactivity increases in the order D-glucose < D-galactose < D-mannose < D-xylose < n-arabinose < D-ribose < D-lyxose. ... 

Sugars differ in their tendency to combine with silica. Holzapfel (173, 276) found that galactose was adsorbed on quartz and reacted with phenylhydrazOne and formed osazones, but arabinose did not. The amount of adsorbed galactose was twice that of lactose and four times that of glucose. 

The 2,4-dichlorophenylhydrazones of a great many sugars were isolated and characterized by Mandl and Neuberg (29), The hydrazones were easy to crystallize and gave good melting points. The same authors were able to differentiate between L-arabinose and D-ribose by means of their di-phenylhydrazones. Reactions with p-bromophenylhydrazine or 1-benzyl-l-phenylhydrazine also often lead to crystalline derivatives. 

H]-Biopterin (97), required for metabolism studies, was synthesised by reaction of the phenylhydrazone of 5-deoxy-[5- H]-L-arabinose (see chapter 12) with 2,5,6-triaminopyrimidin-4-one. The same reaction applied to the semicarbazones of pentoses proceeded regiospecifically to yield D-anapterin (98) and L-primapterin (99), which have the polyhydroxyalkyl substituent in a different position on the pteridinone ring. Condensation of 2-methylthio-4,5,6-triamino-pyrimidine with pentose phenylhydrazones yielded triqrclic adducts such as the crystalline product (100) obtained from D-arabinose . 

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