TY - JOUR
T1 - Axial chirality originating in amide and sulfonamide structures
T2 - Flexible stereochemistry of benzo-fused seven-membered-ring heterocycles
AU - Tabata, Hidetsugu
AU - Yoneda, Tetsuya
AU - Takahashi, Hideyo
AU - Natsugari, Hideaki
PY - 2016
Y1 - 2016
N2 - The benzo-fused seven-membered-ring nitrogen heterocycles (e.g., 1-benzazepine, 1,5-benzodiazepine, and 1,5-benzothiazepine), which have been used as important core structures of various biologically active molecules, possess a flexible stereochemical (conformational) nature. When exerting biological activity, the receptors and enzymes should recognize the specific conformation of the heterocycles. Conformational change may cause chirality due to the axis. This article describes such axial chirality originating in amide and sulfonamide structures in relation to biological activity Conformation of the benzo-fused seven-membered-ring was frozen by introducing a methyl group at the peri-position of the benzene ring to enable separation of the (aS)/(aR)-axial isomers originating in the sp2-sp2 axis of the Ar-N(CO) and Ar-N(SO2) moieties. Thus, the conformational and atropisomeric properties of 1N-benzoyl-1,5-benzodiazepine (A), 1,5-benzothiazepin-4-one and its S-oxide (B), N-benzoyl-1,5-benzothiazepine and its S-oxide (C), and 1 N-sulfonyl-1,5-benzodiazepine (D) were clarified. In addition, A and C were evaluated as vasopressin receptor ligands to identify the active conformation recognized by the receptor.
AB - The benzo-fused seven-membered-ring nitrogen heterocycles (e.g., 1-benzazepine, 1,5-benzodiazepine, and 1,5-benzothiazepine), which have been used as important core structures of various biologically active molecules, possess a flexible stereochemical (conformational) nature. When exerting biological activity, the receptors and enzymes should recognize the specific conformation of the heterocycles. Conformational change may cause chirality due to the axis. This article describes such axial chirality originating in amide and sulfonamide structures in relation to biological activity Conformation of the benzo-fused seven-membered-ring was frozen by introducing a methyl group at the peri-position of the benzene ring to enable separation of the (aS)/(aR)-axial isomers originating in the sp2-sp2 axis of the Ar-N(CO) and Ar-N(SO2) moieties. Thus, the conformational and atropisomeric properties of 1N-benzoyl-1,5-benzodiazepine (A), 1,5-benzothiazepin-4-one and its S-oxide (B), N-benzoyl-1,5-benzothiazepine and its S-oxide (C), and 1 N-sulfonyl-1,5-benzodiazepine (D) were clarified. In addition, A and C were evaluated as vasopressin receptor ligands to identify the active conformation recognized by the receptor.
KW - 1,5-benzodiazepine
KW - 1,5-benzothiazepine
KW - Amide
KW - Axial chirality
KW - Sulfonamide
KW - Sulfoxide
KW - Vasopressin receptor
UR - http://www.scopus.com/inward/record.url?scp=84961718324&partnerID=8YFLogxK
U2 - 10.5059/yukigoseikyokaishi.74.56
DO - 10.5059/yukigoseikyokaishi.74.56
M3 - 総説
AN - SCOPUS:84961718324
SN - 0037-9980
VL - 74
SP - 56
EP - 68
JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
IS - 1
ER -