Highly Diastereoselective Intramolecular [1,2]-Stevens Rearrangements—Asymmetric Syntheses of Functionalized Isopavines as Morphinomimetics

Hanessian, Stephen; Mauduit, Marc

doi:10.1002/1521-3773(20011015)40:20<3810::aid-anie3810>3.0.co;2-8

Cited by 35 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar rearrangements of the internal quaternary salts formed from 70b and 70c affords the more complex isopavines 72 and 73 respectively. 105…”

Section: Pavines and Isopavinesmentioning

confidence: 99%

β-Phenylethylamines and the isoquinoline alkaloids

Bentley

2003

Nat. Prod. Rep.

View full text Add to dashboard Cite

This review covers beta-phenylethylamines and isoquinoline alkaloids and compounds derived from them, including further products of oxidation, condensation with formaldehyde and rearrangement, some of which do not contain an isoquinoline system, together with naphthylisoquinoline alkaloids, which have a different biogenetic origin. The occurrence of the alkaloids, with the structures of new bases, together with their reactions, syntheses and biological activities are reported. The literature from July 2001 to June 2002 is reviewed, with 581 references cited.

show abstract

“…Similar rearrangements of the internal quaternary salts formed from 70b and 70c affords the more complex isopavines 72 and 73 respectively. 105…”

Section: Pavines and Isopavinesmentioning

confidence: 99%

β-Phenylethylamines and the isoquinoline alkaloids

Bentley

2003

Nat. Prod. Rep.

View full text Add to dashboard Cite

show abstract

“…Much like eye-teasing Dalièsque paintings of motifs that are “the same and not the same, the surrealism of molecular similarities and of pharmacophore juxtapositions can be just as intriguing. The isopavines, readily available from the corresponding dihydromethanodibenzoazocines (see below), − represent examples of rigid molecules, with exquisitely deployed topology and functionality anchored around a tertiary nitrogen atom originally derived from a natural amino acid. Thus, the isopavine prepared from d -alanine is shown in two perspective drawings represented by A and A ‘ (Figure ).…”

Section: Morphinomimetic Design Through Visual Imagerymentioning

confidence: 99%

The Power of Visual Imagery in Drug Design. Isopavines as a New Class of Morphinomimetics and Their Human Opioid Receptor Binding Activity

et al. 2002

Self Cite

View full text Add to dashboard Cite

The importance of visual imagery and relational thinking manifests itself in a heuristic approach to the design and synthesis of potential morphinomimetics as agonists of the human mu receptor. The well-known class of alkaloids represented by the isopavine nucleus has a topological resemblance to the morphine skeleton, especially when viewed in a particular way. Enantiopure isopavines can be readily obtained from a 1,2 Stevens rearrangement of 13-substituted dihydromethanodibenzoazocines, prepared in four steps from d- and l-amino acids. Consideration of the topology and the expected orientation of the nitrogen lone pair for a better overlap with morphine necessitates the utilization of d-amino acids. By variation of the substituents on the aromatic rings and a judicious choice of ring substituents, it is possible to obtain low nanomolar binding to the human mu receptor while maintaining good to excellent mu/delta selectivity. Agonist-like activity is indicated in a functional assay for one of the analogues originally derived from d-alanine as a precursor. X-ray crystal structures of several compounds corroborate stereochemistries and overall topologies.

show abstract

“…The advances made in asymmetric catalytic synthesis to forge new carbon-carbon bonds with high levels of stereoselectivity have provided access to chiral molecular scaffolds that are ubiquitous in organic functional materials, pharmaceuticals, and natural products. 1 Isopavine alkaloids [2][3][4][5] represent a diverse family of alkaloids that commonly have been isolated from a widespread series of natural sources, exhibiting remarkable biological properties (Figure 1a). 6 From a synthetic standpoint, the enantioselective enolate arylation would provide a simple and straightforward approach to generate key structural motifs I with α,α-diaryl tertiary chiral carbon centers in a stereoselective manner.…”

Section: Introductionmentioning

confidence: 99%