Diversity-Oriented Synthesis and Biological Evaluation of Iminosugars from Unprotected 2-Deoxy-d-ribose

• Published in: European journal of organic chemistry Vol. 2016; no. 21; pp. 3642 - 3649
• Main Authors: Malinowski, Maciej, Rowicki, Tomasz, Guzik, Patrycja, Wielechowska, Monika, Sobiepanek, Anna, Sas, Wojciech
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 01.07.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Biological activity; Carbohydrates; Chemistry; Chemistry, Organic; Cycloaddition; Iminosugars; Nitrogen heterocycles; Nitrones; Physical Sciences; Science & Technology; Carbohydrates; Iminosugars; PHARMACOLOGICAL CHAPERONES; AQUEOUS-MEDIA; C-GLYCOSIDES; SUGARS; Biological activity; Nitrones; CONVENIENT ROUTE; Cycloaddition; Nitrogen heterocycles; GALACTOSIDASE INHIBITORS; CHEMICAL-SYNTHESIS; CHAIN ELONGATION; METAL; DERIVATIVES
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201600459

An exceptionally short synthesis of novel indolizidine‐, quinolizidine‐, and piperidine‐based iminosugars from unprotected 2‐deoxy‐d‐ribose by intramolecular 1,3‐dipolar cycloaddition of sugar‐derived N‐(3‐alkenyl)nitrones has been accomplished. The use of the 2‐deoxy carbohydrate also enabled us to confirm the previously proposed mechanism for the alteration of the stereochemical course of the intramolecular 1,3‐dipolar cycloaddition observed for an unprotected sugar‐derived nitrone. Biological assays of the six new iminosugars revealed a slight inhibition activity of the indolizidine derivative 7a, whereas, interestingly, the two quinolizidine iminosugars 5a and 5b appeared to be weak glycosidase activators. The diversity‐oriented synthesis of iminosugars with various heterocyclic cores has been achieved starting from 2‐deoxy‐dribose with no need for sugar protection in any step. Selective cleavage of the triol to the α‐hydroxy aldehyde with no racemization of the α‐stereocenter was accomplished with 1 equiv. of sodium periodate at low temperature.