Qualitative evaluation of regioselectivity in the formation of di- and tri-6-O-tritylates of α-cyclodextrin.

The quantitative analysis of reaction products showed that the reaction of 6(A),6(D)-di-O-trityl-α-cyclodextrin (CD), AD-isomer, with trityl chloride in pyridine at 55 °C gave 6(A),6(B),6(E)-tri-O-trityl-α-CD, the amount of which was only 25% of that of simultaneously formed 6(A),6(B),6(D)-tri-O-trityl-α-CD. This indicates that the bulky trityl groups of glucopyranose-A and -D (Glu-A and -D, respectively) in the AD-isomer mainly retard the additional tritylation of the C(6)-OH of the adjacent glucopyranoses in a counter-clockwise direction (Glu-F and -C, respectively). (1)H NMR spectra of the AD-isomer showed that the O(6)-H and C(6)-H signals of Glu-C and -F are shifted upfield due to the ring current of the trityl groups. Thus, it is concluded that the bulky trityl groups on Glu-A and Glu-D are oriented to Glu-F and Glu-C, respectively, and sterically retard additional tritylation on Glu-F and Glu-C. Similar steric hindrance was also observed in the additional tritylations of mono-6-O-trityl-α-CD, 6(A),6(B)-di- and 6(A),6(C)-di-O-trityl-α-CD's.