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Seven‐Step Synthesis of All‐Nitrogenated Sugar Derivatives Using Sequential Overman Rearrangements
Author(s) -
Okuyama Yuya,
Kidena Mayu,
Kato Erina,
Kawano Sayaka,
Ishii Koki,
Maie Kenta,
Miura Kazuki,
Simizu Siro,
Sato Takaaki,
Chida Noritaka
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202015141
Subject(s) - monosaccharide , chemistry , glycosylation , chirality (physics) , organic chemistry , silylation , combinatorial chemistry , cytotoxicity , carbohydrate , stereochemistry , biochemistry , catalysis , in vitro , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
All‐nitrogenated sugars (ANSs), in which all hydroxy groups in a carbohydrate are replaced with amino groups, are anticipated to be privileged structures with useful biological activities. However, ANS synthesis has been challenging due to the difficulty in the installation of multi‐amino groups. We report herein the development of a concise synthetic route to peracetylated ANSs in seven steps from commercially available monosaccharides. The key to success is the use of the sequential Overman rearrangement, which enables formal simultaneous substitution of four or five hydroxy groups in monosaccharides with amino groups. A variety of ANSs are available through the same reaction sequence starting from different initial monosaccharides by chirality transfer of secondary alcohols. Transformations of the resulting peracetylated ANSs such as glycosylation and deacetylation are also demonstrated. Biological studies reveal that ANS‐modified cholesterol show cytotoxicity against human cancer cell lines, whereas each ANS and cholesterol have no cytotoxicity.