Reaction of PQQ with L-Tryptophan

Pyrroloquinolinequinone (PQQ, 1) is one of a number of o-quinones which serve as prosthetic groups in quinoproteins, and has been the subject of intense interest because of its growth-stimulating, pharmaceutical and nutritional activities (c.f. Problem number 41). There is also considerable interest in the in vitro reactions of PQQ with biomolecules, and in this context the reaction of PQQ with L-tryptophan in phosphate buffer (pH 6.5) under aerobic conditions was investigated. This gave three products 2, 3 and 4, with 2 the major component. Compounds 2 and 4 showed a much more pronounced growth-stimulating effect than PQQ, while 3 also showed a marked effect . 

Give mechanisms for the reaction of 1 with L-tryptophan to produce 2,3 and 4. 

An Unexpected Result from an Attempted Double Bischler-Napieralski Reaction 

As part of a programme designed to produce compounds with axial chirality, double Bischler-Napieralski reactions were carried out with oxamide derivatives of co-arylalkylamines. Thus, treatment of the oxamide derived from 3,4-dimethoxy- P -pheny lethylamine with pyrophosphoryl chloride in acetonitrile gave 1 in 84% yield, as expected. An attempt was then made to extend this double cyclisation protocol to the oxamide derived from 2-(3-methoxyphenoxy)ethylamine. Reaction of this latter compound under the same conditions used for the formation of 1, however, gave 2 in 81% yield instead of the expected product of a double Bischler-Napieralski reaction. 

The biosynthesis of many bis-indole alkaloids has been postulated to proceed by dimerisation of appropriate precursors, and there is now a substantial amount of experimental evidence to support this hypothesis. For example, treatment of the alcohol 1 with acid gives the alkaloid yuehchukene 2, and 1 could arise biogenetically by in vivo prenylation of indole followed by enzymatic oxidation. A study of related 2-prenylated indoles has confirmed the ease with which such molecules can dimerise . Thus, treatment of the secondary alcohol 3 in benzene with silica gel impregnated with TsOH gave a complex mixture of products from which 4 (5.1%) and 5 (2.1%) were isolated (3 is very sensitive to acid, and is easily decomposed). Treatment of the isomeric tertiary alcohol 6 with a catalytic amount of TFA in anhydrous benzene gave much higher yields of the two dimeric products 7 (31%) and 8 (25%). 

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