Flavin synthetic analogs

Many other redox reactions are potentially amenable to antibody catalysis. For example, the chemistry of the P-450 cytochromes, including the hydroxylation of alkanes and the epoxidation of alkenes, can be mimicked with synthetic porphyrins. Incorporation of such molecules into antibody active sites could conceivably yield new catalysts that combine the intrinsic reactivity of the cofactor with the tailored selectivity of the binding pocket. Work is just beginning in this area, but preliminary studies with porphyrin haptens have yielded some interesting results.126-130 Novel redox chemistry can also be anticipated for antibodies containing metal ions, flavins, nicotinamide analogs, and other reactive moieties. 

An initial summary of the nature and scope of redox processes involving flavin coenzymes will be presented to set the framework for evaluation of the utility of the specific coenzyme analogs. Analogs altered atN(5), atN(l), or atN(l) andN(5) by synthetic substitution of carbon will be discussed before analysis of 8-demethyl-8-hydroxy analogs either with nitrogen or carbon at the 5 position. 

The aims of the modification of flavin-based compounds are to investigate the interaction of these flavin analogs with their reconstituted proteins and to understand their catalytic mechanism. Synthetic flavin analogs serve as active-site probes for almost all positions of the flavin nucleus. ... 

Subsequently, 8-nor-8-hydroxy-flavin compounds were synthetized by an analogous procedure and were shown to simulate the spectral parameters of the natural product at the riboflavin level as, for example, in the ESR (Fig. 3), the pH dependence of fluorescence emission and absorption spectra. Thus the structure of the orange chromophore was established as the 8-nor-8-hydroxy-derivative of FAD (18, R = Rib-( )-AMP). Alternatively, a hydroxy function can be introduced into position 8 of the flavin ring by hydrolysis of 8-nor-8-diazonium-flavin compounds 152). 

A closely related flavin has been found in cultures of Streptomyces davawensis by Japanese researchers. The structure of this compound, which was called roseoflavin because of its deep red colour (abs. max. 496 nm), was ascertained by oxidative degradation of the ribityl side chain and subsequent X-ray crystallography of the 2 -acetyl derivative (130). It represents the 8-nor-8-dimethylamino derivative of riboflavin (19) and is thus an analog of 8a-aminoflavin types synthetized earlier by Hemmerich et al at the lumiflavin (75) and Berezowskii at the riboflavin level (5). 

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