TY - JOUR
T1 - Conformational spaces of Cinchona alkaloids
AU - Caner, Hava
AU - Biedermann, P. Ulrich
AU - Agranat, Israel
PY - 2003
Y1 - 2003
N2 - A systematic and comprehensive study of the conformational spaces of the Cinchona alkaloids quinine, quinidine, cinchonine, cinchonidine, epiquinine, epiquinidine, epicinchonine, and epicinchonidine using the semiempirical PM3 method is described. The results were analyzed in terms of syn/anti and open/closed/hindered and α/β/γ conformations. Special emphasis was given to the torsion angles T2 (C4a′-C4′-C9-C8), T2 (C4′-C9-C8-N1) and T3 (H-O9-C9-C8) that define the backbone and the hydroxy conformation, respectively. The results reveal the quasi-enantiomeric relationships between quinine and quinidine and between epiquinine and epiquinidine, and the main structural differences that exist between the therapeutically active Cinchona alkaloids, quinine and quinidine, and their inactive epimers, epiquinine and epiquinidine. The lowest energy conformation of quinine and quinidine is anti-closed-α. The lowest energy conformations of epiquinine and epiquinidine are anti-open-β and anti-open-α, respectively. Low energy conformations with an intramolecular hydrogen bond (N1⋯H⋯O9) were found in epiquinine (the global minimum) and epiquinidine, but not in quinine and quinidine.
AB - A systematic and comprehensive study of the conformational spaces of the Cinchona alkaloids quinine, quinidine, cinchonine, cinchonidine, epiquinine, epiquinidine, epicinchonine, and epicinchonidine using the semiempirical PM3 method is described. The results were analyzed in terms of syn/anti and open/closed/hindered and α/β/γ conformations. Special emphasis was given to the torsion angles T2 (C4a′-C4′-C9-C8), T2 (C4′-C9-C8-N1) and T3 (H-O9-C9-C8) that define the backbone and the hydroxy conformation, respectively. The results reveal the quasi-enantiomeric relationships between quinine and quinidine and between epiquinine and epiquinidine, and the main structural differences that exist between the therapeutically active Cinchona alkaloids, quinine and quinidine, and their inactive epimers, epiquinine and epiquinidine. The lowest energy conformation of quinine and quinidine is anti-closed-α. The lowest energy conformations of epiquinine and epiquinidine are anti-open-β and anti-open-α, respectively. Low energy conformations with an intramolecular hydrogen bond (N1⋯H⋯O9) were found in epiquinine (the global minimum) and epiquinidine, but not in quinine and quinidine.
KW - Epiquinidine
KW - Epiquinine
KW - Quasienantiomers
KW - Quinidine
KW - Quinine
KW - Semiempirical study
UR - http://www.scopus.com/inward/record.url?scp=0041663651&partnerID=8YFLogxK
U2 - 10.1002/chir.10265
DO - 10.1002/chir.10265
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C2 - 12840830
AN - SCOPUS:0041663651
SN - 0899-0042
VL - 15
SP - 637
EP - 645
JO - Chirality
JF - Chirality
IS - 7
ER -