Structure and absolute configuration of a high affinity 5-HT3 receptor antagonist, (5aS,9aS)-N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2-chloro- 5a,6,7,8,9,9a-hexahydro-4-dibenzofurancarboxamide hydrochloride.
The absolute configuration was established as (S,S,S) by the R-factor test and by careful measurement of 197 enantiomorph-sensitive Friedel pairs of reflections. The determination also confirms the absolute stereochemistry of (-)-3-aminoquinuclidine, a compound used in the preparation of the title material. The cyclohexane/tetrahydrofuran ring fusion is cis. The quinuclidine moiety has almost perfect threefold symmetry; the front and rear halves are twisted about this axis by 15 degrees. Quinuclidine-N--H ... Cl- and amide-N--H ... Cl- hydrogen bonds link screw-dyad-related molecules along the b axis.
Ammon
H L
HL
Department of Chemistry and Biochemistry, University of Maryland, College Park 20742.
Youssefyeh
R D
RD
Airey
J E
JE
Studt
W L
WL
Campbell
H F
HF
Powers
M R
MR
Golec
F A
FA
D000577:Amides / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008968:Molecular Conformation; D012702:Serotonin Antagonists / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; C073524:N-(1-azabicyclo(2.2.2)octan-3-yl)-8-chloro-2,6-methano-3,4,5,6-tetrahydro-2H-1-benzoxocin-10-carboxamide