1509-00-8Relevant articles and documents
Antipodal α-N-(methyl through decyl)-N-normetazocines (5,9α-dimethyl- 2'-hydroxy-6,7-benzomorphans): In vitro and in vivo properties
May,Aceto,Bowman,Bentley,Martin,Harris,Medzihradsky,Mattson,Jacobson
, p. 3408 - 3418 (1994)
The enantiomeric (-)- and (+)-N-(methyl through decyl) normetazocines (5,9α-dimethyl-2'-hydroxy-6,7-benzomorphans) were synthesized and their in vitro and in vivo activities determined. Increasingly bulky enantiomeric N- alkyl homologs were prepared until their interaction with the σ1 receptor decreased and their insolubility became a hindrance to their evaluation in vivo and/or in vitro. The (-)-methyl, -pentyl, -hexyl, and -heptyl homologs were essentially as potent as, or more potent than, morphine in the tail- flick, phenylquinone, and hot-plate assays for antinociceptive activity; the (-)-propyl homolog had narcotic antagonist activity between that of nalorphine and naloxone in the tail-flick vs morphine assay, and it also displayed antagonist properties in the single-dose suppression assay in the rhesus monkey. The antinociceptively potent (-)-heptyl homolog did not substitute for morphine in monkeys but did show morphine-like properties in a primary physical-dependence study in continuously infused rats. All five potent compounds showed high affinity for the μ opioid receptor from both rat and monkey preparations and the κ opioid receptor (0.05 μM), and all except the (-)-methyl homolog interacted reasonably well at the δ receptor (K(i) 0.1 μM). The (-)-propyl compound was equipotent (K(i) 1.5-2.0 nM) at μ and κ receptors. The pattern of interaction of the (-)-enantiomeric homologs with μ receptors from rat and monkey preparations was similar, but not identical. The enantioselectivity of the homologs for μ receptors was greater in the rat than in the monkey preparation for all but the N-H and butyl compounds, and the enantioselectivity of the lower homologs (methyl through butyl) for the μ (monkey) receptor was greater than for the κ or δ receptors. However, bulkier homologs (hexyl through decyl) displayed higher enantioselectivity at κ or δ receptors than at the μ (monkey) receptor. The (+)-butyl through (+)-octyl homologs were essentially equipotent with, or more potent than, (+)-pentazocine at the σ receptor. Only the (+)-H and (+)- methyl homologs had high affinity (0.05 μM) at PCP binding sites.
Saito,May
, p. 1087 (1962)
Migratory hydroamination: A facile enantioselective synthesis of benzomorphans
Trost, Barry M.,Tang, Weiping
, p. 8744 - 8745 (2007/10/03)
We describe a highly efficient, general strategy for the enantioselective synthesis of benzomorphans (45-46% overall yield from commercially available material). The new synthesis demonstrates the effectiveness of an unprecedented diastereoselective cycloisomerization via migratory hydroamination and the power of palladium-catalyzed asymmetric allylic alkylation (AAA) of simple ketone enolates in the context of complex synthesis. The strategy outlined here for the enantioselective synthesis of three contiguous stereogenic centers and the novel cycloisomerization should have many applications in alkaloid synthesis. Copyright
An improved resolution of (±)-cis-N-normetazocine
Brine,Berrang,Hayes,Carroll
, p. 2139 - 2143 (2007/10/02)
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