4 research outputs found
<i>N</i>‑Benzoyl-1,5-benzothiazepine and Its <i>S</i>‑Oxide as Vasopressin Receptor Ligands: Insight into the Active Stereochemistry around the Seven-Membered Ring
The stereochemistry of <i>N</i>-benzoyl-1,5-benzothiazepine
and its <i>S</i>-oxide derivatives as vasopressin receptor
ligands was examined in detail by freezing the conformation with a
methyl group at the C6 or C9 of 1,5-benzothiazepine. It was revealed
that the active forms recognized by the receptors are (<i>cis</i>,a<i>S</i>) for 1,5-benzothiazepine (<b>5</b>–<b>7</b>)-<b>II</b> and (<i>cis</i>,1<i>S,</i>a<i>S</i>) (<i>syn</i>) for its <i>S</i>-oxide (<b>8</b>–<b>10</b>)-<b>II</b>. The
C9-methyl derivative of 1,5-benzothiazepine <i>S</i>-oxide
(<b>10</b>-<b>II</b>) was designed and synthesized, achieving
the putative active <i>syn</i>-isomer
<i>N</i>‑Benzoyl- and <i>N</i>‑Sulfonyl-1,5-benzodiazepines: Comparison of Their Atropisomeric and Conformational Properties
The atropisomeric and conformational
properties of 1,5-benzodiazepines
with an <i>N</i>-sulfonyl (<i>p</i>-tosyl/mesyl)
group (<b>IIa</b>/<b>b</b>) were investigated by comparison
with those of the <i>N</i>-benzoyl congeners (<b>I</b>). Similar to <b>I</b>, when the Ar–NÂ(SO<sub>2</sub>) axis was frozen by a C9-substitution in the molecules, <b>IIa</b>/<b>b</b> were separated into the (a<i>R</i>)- and
(a<i>S</i>)-atropisomers. The conformation of <b>IIa</b>/<b>b</b> revealed that the substituent (<i>p</i>-tolyl/methyl group) in the sulfonyl moiety occupies the position
over the diazepine ring (folded form) in both the solid and solution
states [e.g., (+)-(a<i>R</i>)-<i>N</i>-<i>p</i>-tosyl<b>-</b>1,5-benzodiazepin-2-one (<b>IIa-2</b>)], whereas that of <b>I</b> is <i>anti</i> to the
diazepine ring [e.g., (−)-(a<i>R</i>)-<i>N</i>-benzoyl<b>-</b>1,5-benzodiazepin-2-one (<b>I-2</b>)],
which was further supported by a computational study. The stereochemical
stability also differed between the two congeners (e.g., Δ<i>G</i><sup>⧧</sup>: 104 kJ/mol for <b>I-2</b> and
132 kJ/mol for <b>IIa-2</b>)
Stereochemistry of <i>N</i>‑Benzoyl-5-substituted-1-benzazepines Revisited: Synthesis of the Conformationally Biased Derivatives and Revision of the Reported Structure
The <i>syn</i> (a<i>R</i>*,5<i>R*</i>) and <i>anti</i> (a<i>S</i>*,5<i>R*</i>) diastereomers of <i>N</i>-benzoyl-C5-substituted-1-benzazepines
originating in the chiralities at C5 and the Ar–NÂ(Cî—»O)
axis were first stereoselectively synthesized by biasing the conformation
with a substituent at C6 and C9, respectively. Detailed examination
of the stereochemistry (i.e., conformation and configuration) of these <i>N</i>-benzoyl-1-benzazepines by X-ray crystallographic analysis,
VT NMR, and DFT calculations revealed new physicochemical aspects
of these heterocycles including revision of the stereochemistry previously
reported
A Complete Gear System in <i>N</i>‑Benzoyl-Carbazole Derivatives
2′,6′-Disubstituted <i>N</i>-benzoylated
carbazole derivatives were found to exhibit atropisomerism. The bulky
substituents restricted rotation about the N–C7′ and
C7′–C1′ bonds to separate four atropisomers,
in which rotation about the C7′–C1′ bond was
in perfect concert with rotation about the N–C7′ bond.
Complete geared rotation without slippage at 37 °C for 7 days
was observed for the first time. Conformational analysis clarified
the preference for the gear system over other internal conversion
pathways