Model Chemistry of Tryptophan Tryptophylquinone Cofactor

This report covers the model chemistry conducted on the tryptophan tryptophylquinone (TTQ) cofactor 1. The synthesis of the TTQ model compound 13 was established and optimised, starting from o-anisidine (40). Different strategies were attempted to increase the yield of indole-ester compound 42, which was the lowest yielding reaction (38%) in the synthesis of the TTQ model compound 13. The electronic effects on the catalytic oxidation of p-substituted benzylamines by the TTQ model compound 13 have been studied. The TTQ model compound 13 was found to act as an efficient catalyst for the formation of imines 35, 76 and 82. The electronic effect on the aerobic oxidation of p-substituted benzylamines 72, 74 and 80 by TTQ model compound 13 was found to be minimal. The KIEs for benzylamine oxidation by the TTQ model compound 13 have also been investigated. The apparently very large KIE of 48 indicated that the reaction when deuterated benzylamine (87) was used is proceeding slower than expected, compared to the KIE of 9.2 observed by Itoh and co-workers.36 A possible route to a water-soluble derivative of the TTQ model compound 13 has been investigated. The aqueous solubility of the indole 89 was found to be sufficient for the proposed kinetic studies to be carried out using the indole-quinone 91, which is derived from indole 89. Possible routes to the syntheses of other TTQ analogues have also been investigated. A major synthetic achievement was the faster and more efficient synthesis of the TTQ analogue 36 than that reported by Itoh and coworkers. 34, 40 The synthesis of the TTQ analogue 101 was two-steps from completion and the synthesis of the TTQ analogue 102 was three-steps from completion.