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-cysteinyidopa (1), L-alpha-methyldopa (2) and DL-m-tyrosine (3) with D-glucose were investigated at 90 degrees 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 beta-D-fructopyranosyl and alpha,beta-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 I R 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.