Final Thoughts on Chemistry for (2R,3R,4S,5S,6S)-2-Hydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

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beta-Glucuronyl carbamate based pro-moieties designed for prodrugs in ADEPT

A number of pro-moieties 8a-e designed for prodrug preparation have been synthesized. The pro-moieties, containing a glucuronyl carbamate group linked to a spacer possessing a terminal carboxylic acid group, have been synthesized from isocyanates 6 and anomerically unprotected glucuronic acids 10. The requisite isocyanates had to be prepared using the Curtius rearrangement. Glucuronyl carbamates proved to be excellent substrates for human beta-glucuronidase. The pro-moieties 8a-e can be coupled to hydroxy- or amino group containing drugs. The resulting prodrugs are designed to be activated by beta-glucuronidase and to be used in ADEPT. Application is demonstrated with the synthesis of duanomycin prodrugs 12a-e.

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Reference:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics