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Probes for Narcotic Receptor Mediated Phenomena
Author(s) -
Linders Joannes T. M.,
Mirsadeghi Seid,
FlippenAnderson Judith L.,
George Clifford,
Jacobson Arthur E.,
Rice Kenner C.
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390048
Subject(s) - chemistry , piperidine , stereochemistry , dihedral angle , ring (chemistry) , molecule , crystallography , hydrogen bond , organic chemistry
The synthesis of a series of epoxy 5‐phenylmorphans is being explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan molecule that may be needed both for binding to a specific opioid receptor and for exhibiting opioid agonist or antagonist activity. Of the twelve possible ortho ‐ and para ‐bridged isomers (a–f) ( Fig. 1 ), we now report the synthesis of the para ‐d isomer, rac ‐(3 R ,6a S ,11a R )‐2‐methyl‐1,3,4,5,6,11a‐hexahydro‐2 H ‐3,6a‐methanobenzofuro[2,3‐ c ]azocin‐8‐ol ( 3 ). Compound 3 was synthesized via construction of the 5‐phenylazabicyclo[3.3.1]non‐3‐ene skeleton ( Scheme 1 ) and subsequent closure of the epoxy bridge ( Scheme 2 ). As determined by an X‐ray diffraction study, the epoxy bridge, restricting the phenyl‐ring rotation, fixed the dihedral angle between the least‐squares planes through the phenyl ring and atoms N(2), C(3), C(11a), and C(6a) of the piperidine ring ( Fig. 2 ) at 43.0°, and the torsion angle C(12)C(6a)C(6b)C(10a) at −95.0°.