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Chemoenzymatic Synthesis of Hygromycin Aminocyclitol Moiety and its C2 Epimer
Author(s) -
Carrau Gonzalo,
Bellomo Ana Inés,
Suescun Leopoldo,
Gonzalez David
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801424
Subject(s) - aminocyclitol , chemistry , moiety , epimer , stereochemistry , enantioselective synthesis , chirality (physics) , total synthesis , ring (chemistry) , combinatorial chemistry , organic chemistry , catalysis , aminoglycoside , biochemistry , antibiotics , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
This manuscript describes the enantioselective synthesis of the aminocyclitol moiety of the antibiotic hygromycin A in eight steps and 39 % overall yield from a non‐chiral starting material. The sequence made use of an initial enzymatic step to transfer chirality to an aromatic ring and was followed by selective organic chemistry transformations (oxidation, protection, azidation, hydrolysis) of the six‐membered ring in order to achieve the target. The approach is also amenable to the synthesis of other related unnatural analogues as exemplified by the synthesis of the C2 epimer of the natural aminocyclitol. All the intermediates were fully characterized, and the absolute stereochemistry assigned by spectrometric methods.