[1,4]-sigmatropic rearrangement of chiral nitrones and their utilization in the synthesis of new iminosugars

• Published in: Organic & biomolecular chemistry 2016-01, Vol.14 (2), p.470-482
• Main Authors: Malinowski, Maciej, Rowicki, Tomasz, Guzik, Patrycja, Gryszel, Maciej, Łapczyński, Sebastian, Wielechowska, Monika, Czerwińska, Karolina, Madura, Izabela, Sas, Wojciech
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glucosidases - antagonists & inhibitors; Glucosidases - metabolism; Humans; Imino Sugars - chemical synthesis; Imino Sugars - chemistry; Imino Sugars - pharmacology; Models, Molecular; Molecular Structure; Nitrogen Oxides - chemistry; Quantum Theory; Stereoisomerism; Structure-Activity Relationship; Thermodynamics
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01432h

Reflection on the epimerization of the α-stereocenter of sugar nitrones leads to the conclusion that the process may occur through [1,4]-sigmatropic rearrangement. Participation of an ionic mechanism was excluded by a deuterium labeling experiment, and DFT calculations showed a reasonable energy barrier for the proposed [1,4]-shift. Products of the intramolecular 1,3-dipolar cycloaddition of the studied nitrones were utilized in the diversity-oriented synthesis of polyhydroxy derivatives of piperidine, indolizidine and quinolizidine. Minimal activity against the screened glucosidases and human melanoma cell lines was observed for some of the obtained compounds.