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Aminoglycoside Antibiotics – Fortamine Aglyca Total Synthesis, Optical Resolution, Chemical Modifications
Author(s) -
Schubert Jürgen,
Schwesinger Reinhard,
Knothe Lothar,
Prinzbach Horst
Publication year - 1986
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.198619861201
Subject(s) - chemistry , diastereomer , total synthesis , epoxide , stereochemistry , resolution (logic) , aminoglycoside , adduct , benzene , antibiotics , organic chemistry , biochemistry , catalysis , artificial intelligence , computer science
Starting from the dianhydro‐ epi ‐inositol 10 (available ultimately from benzene) an expedient total synthesis of enantiomerically pure (+)/(−)‐de‐ O ‐methylfortamines (derivatives) has been developed. Key steps are the regiospecific epoxide openings which occur intramolecularly in the diepoxybis(urethane) 11 and intermolecularly by (+)‐1‐phenylthylamine in the epoxyurethanes rac ‐ 13 . The diastereomeric adducts ( 30, 32 ) are quantitatively separated by crystallization/chromatogrphy. Following hydrogenation, natural and nonnatural cis ‐1,4‐inosadiamines are obtained optically pure [e.g. fortamine (−)‐ 1 , ent ‐fortamine (+)‐ 1 , 3‐ O ‐demethylfortamine (−)‐ 38 , ent ‐3‐ O ‐demethylfortamine (+)‐ 38 ]. This approach, which was optimized by numerous model reactions, allows wide chemical modifications and leads among others to 3‐ O ‐demethylfortamine and ent ‐fortamine derivatives in which only the (6)4‐OH‐group, the one to be glycosidated, remains unprotected.