Reactions of d-glucose with phenolic amino acids: further insights into the competition between Maillard and Pictet–Spengler condensation pathways

The reactions of 5-S-cysteinyldopa (1), l-α-methyldopa (2) and dl-m-tyrosine (3) with d-glucose were investigated at 90 °C in phosphate buffer at pH ranging from 5.0 to 9.0. Whereas 1 gave mainly the double Maillard condensation product N,N′-bis(1″-deoxy-d-fructos-1″-yl)-5-S-cysteinyldopa, as an inseparable mixture of β-d-fructopyranosyl and α,β-d-fructofuranosyl derivatives, 2 and 3 gave both Maillard and Pictet–Spengler products, although to different extents and with different regio- and stereochemistry. A peculiar pattern of reactivity was displayed by 2 which gave, besides the Maillard product and the expected 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline C-1 diastereoisomeric pairs, the unprecedented 7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline derivative via the ortho cyclization pathway. Pictet–Spengler cyclization of 2 and 3 proceeded with Felkin–Anh-type asymmetric induction, favouring the 1R isomer throughout the pH range 5.0–9.0. These results, which highlight the first example of carbohydrate-derived 7,8-dihydroxytetrahydroisoquinoline, provide new insights into the factors governing competition between Maillard and Pictet–Spengler condensation pathways.

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