Scheme 24 The deprotection sequence of the HA trimer.
acetal, which was then converted to the corresponding ^-imidate III.5. Alternative treatment of III.17 with hydrogen bromide gave the glycosyl bromide III.6.
Condensation of III.3 with III.5 by means of TMSOTf gave III.18 (75% yield) as the precursor to the 4-O-sulfated chondroitin disaccharide. Similarly, condensation of III.3 with III.6 by means of AgOTf as a promoter also afforded III.18 in 90% yield. The disaccharide precursor to the 6-O-sulfated chondroitin disaccharide (III.19) was also obtained by the use of either glycosyl donor. Glycosylation of III.4 with imidate III.5 or bromide III.6 gave the desired disaccharide III.19 in 72 or 80% yield, respectively. Interestingly, for these specific substrates, the Koenigs-Knorr glycosylations for the preparation of III.18 and III.19 proceeded in higher yield than the corresponding trichloroacetimidate glycosylations.
R1 = S03", R2 = H chondroitin 4-sulfate R1 = H, R2 = S03" chondroitin 6-sulfate R1 = so3-, R2 = SO3- chondroitin 4,6-disulfate
Figure 4 The four possible repeating units of chondroitin sulfate.
Scheme 25 The Jacquinet synthesis of the 4- and 6-O-sulfated chondroitin disaccharides.
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