Pseudobase isomerization

In some cases two isomeric tropones (4-oxo and 6-oxo) and two or more tropilidenes are formed from tropylium salts [66JCS(C)926] or from the equivalent pseudobases (cycloheptatrienols or tropols 69ZOB2601). Finally nucleophilic attack can generate an unstable tropol that yields, on oxidation, the desired tropone (78AJC1607). 

From extensive analysis of recombinant proteins, and the crystal structure of A. thaliana protein, detailed reaction mechanisms have been proposed. The ANS reaction likely proceeds via stereospecific hydroxylation of the leucoanthocyanidin (flavan-3,4-cA-diol) at the C-3 to give a flavan-3,3,4-triol, which spontaneously 2,3-dehydrates and isomerizes to 2-flaven-3,4-diol, which then spontaneously isomerizes to a thermodynamically more stable anthocyanidin pseudobase, 3-flaven-2,3-diol (Figure 3.2). The formation of 3-flaven-2,3-diol via the 2-flaven-3,4-diol was previously hypothesized by Heller and Forkmann. The reaction sequence, and the subsequent formation of the anthocyanidin 3-D-glycoside, does not require activity of a separate dehydratase, which was once postulated. Recombinant ANS and uridine diphosphate (UDP)-glucose flavonoid 3-D-glucosyltransferase (F3GT, sometimes... 

Various isolated examples of pKR + values for other heteroaromatic systems are given in Table I. The similarity in pKR + values for the isomeric 1-, 2-, 3-, and 4-selenaphenanthrene cations further supports the preceding inference that the change in resonance energy upon pseudobase formation is the major determinant of pKR+. 

In the case of azapetine (12) and nicotine (13), the iminium ion intermediate rather than the carbinolamine appears to be the form of substrate preferred by aldehyde oxidase [63-66]. On the other hand, the ring-opened aldehyde intermediate (aldophosphamide) (14) of cyclophosphamide is oxidized by the enzyme [67], although the isomeric 4-hydroxycyclophos-phamide (15) also undergoes oxidation by a soluble fraction enzyme [11]. Oxidation of the carbinolamine form to a cyclic lactam would not seem to involve nucleophilic enzyme attack, and yet we have shown that the stable pseudobase of 3-methylquinazolin-2-one (16), is an efficient substrate of aldehyde oxidase and competitively inhibits the oxidation of both quaternary and non-quatemized substrates [62]. 

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