Azo Compounds.<sup>1</sup> Oxidation of 1,1-Disubstituted Hydrazines. The Synthesis and Oxidation of cis- and trans-1-Amino-2,6-diphenylpiperidine. A New Stereospecific Ring Closure

Overberger, C. G.; Lombardino, Joseph G.; Hiskey, Richard G.

doi:10.1021/ja01581a020

Cited by 28 publications

(3 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initial attempts to reduce this pyridine compound using catalytic hydrogenation led exclusively to cis -piperidine 9a , with no appreciable amounts formed of the trans diastereomer 9b . After evaluating a variety of different conditions, it was found that the Ladenburg reduction − of the pyridine ring led efficiently to the desired pair of diastereomers in a 1.3:1 ratio, favoring the trans isomer. Stoichiometric bromination at 0 °C of the resulting piperidines, 35a and 35b , provided access to the desired products 9a and 9b .…”

Section: Chemistrymentioning

confidence: 99%

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Juncosa

Hansen

Bonner

et al. 2012

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Based on the structure of the superpotent 5-HT 2A agonist 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, which consists of a ringsubstituted phenethylamine skeleton modified with an N-benzyl group, we designed and synthesized a small library of constrained analogues to identify the optimal arrangement of the pharmacophoric elements of the ligand. Structures consisted of diversely substituted tetrahydroisoquinolines, piperidines, and one benzazepine. Based on the structure of (S,S)-9b, which showed the highest affinity of the series, we propose an optimal binding conformation. (S,S)-9b also displayed 124-fold selectivity for the 5-HT 2A over the 5-HT 2C receptor, making it the most selective 5-HT 2A receptor agonist ligand currently known.

show abstract

Section: Chemistrymentioning

confidence: 99%

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Juncosa

Hansen

Bonner

et al. 2012

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In recent years, several reactions involving the removal of a nitrogen moiety from amines with a stoichiometric amount of reagents have been reported. Thermal decomposition of 1,1-diazene, a nitrogen-stabilized nitrene, is known to generate a new C–C bond by breaking two C–N bonds (Scheme A). − If one could generate 1,1-diazene from secondary amines in an efficient manner, then overall nitrogen deletion from secondary amines could be realized. Lu and co-workers reported that sulfamoyl azides 13 , which are synthesized by the reaction of secondary amines 12 with N 3 SO 2 N 3 , can generate 1,1-diazene W via a Curtius-type rearrangement upon heating at 80 °C, which immediately undergoes the elimination of N 2 to forge a new C–C bond (Scheme B) .…”

Section: Elimination Of a Single Atommentioning

confidence: 99%

Unimolecular Fragment Coupling: A New Bond-Forming Methodology via the Deletion of Atom(s)

Shimazumi,

Tobisu

2024

JACS Au

View full text Add to dashboard Cite

Unimolecular fragment coupling (UFC) is defined as a reaction format, wherein atom(s) located in the middle of a molecule are extruded, and the remaining fragments are coupled. UFC is a potentially powerful strategy that is an alternative to transition-metal-catalyzed cross-coupling because the target chemical bond is formed in an intramolecular fashion, which is inherently beneficial for chemoselectivity and stereoselectivity issues. In this Perspective, we will present an overview of the recent advances in UFC reactions, which encompass those proceeding through the elimination of CO 2 , CO, SO 2 , isocyanates, N 2 , or single atoms primarily via transition metal catalysis.

show abstract

“…The hydroxyl moiety was removed with PBr 3 , although this step was only successful in a low yield (40%). The pyridine ring was saturated using Ladenburg conditions, yielding the unfunctionalized compound. − It was discovered that the previous step to remove the benzyl alcohol could be omitted, as treatment with elemental sodium efficiently removed the alcohol and fully saturated the pyridine ring in a single step, giving the cis and trans compounds cis- 6 and trans- 7 in a diasteriomeric ratio of 1:1.2, respectively. The diastereomers were separated by column chromatography and subsequently functionalized at the 4′-position.…”

mentioning

confidence: 99%

Introducing Conformational Restraints on 25CN-NBOH: A Selective 5-HT_2A Receptor Agonist

Märcher-Rørsted

Nykodemová

Harpsøe

et al. 2023

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

The N-benzylphenethylamines (NBOMes) are a class of ligands from which compounds with impressive selectivity for the serotonin 2A receptor (5-HT2AR) over the closely related serotonin 2C receptor (5-HT2CR) have emerged. These include 4-(2-((2-hydroxybenzyl)amino)ethyl)-2,5-dimethoxybenzonitrile (25CN-NBOH, 1) and 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine (DMPMBB, 2). The present work entails the synthesis and characterization of ligands wherein the structures of these two molecules have been fused. The desired compounds were accessed by a six-step synthetic procedure followed by the chiral resolution of the resulting racemic mixtures, giving one active ((S,S)-3) and three essentially inactive stereoisomers. In silico experiments support that one of the four possible stereoisomers would be active. Further in silico investigations showed that 1, 2, and (S,S)-3 share a common binding mode, further supporting the shared stereochemistry between the active enantiomer ((S,S)-3) and 2.

show abstract

Azo Compounds.¹ Oxidation of 1,1-Disubstituted Hydrazines. The Synthesis and Oxidation of cis- and trans-1-Amino-2,6-diphenylpiperidine. A New Stereospecific Ring Closure

Cited by 28 publications

References 2 publications

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Unimolecular Fragment Coupling: A New Bond-Forming Methodology via the Deletion of Atom(s)

Introducing Conformational Restraints on 25CN-NBOH: A Selective 5-HT_2A Receptor Agonist

Contact Info

Product

Resources

About

Azo Compounds.1 Oxidation of 1,1-Disubstituted Hydrazines. The Synthesis and Oxidation of cis- and trans-1-Amino-2,6-diphenylpiperidine. A New Stereospecific Ring Closure

Cited by 28 publications

References 2 publications

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT2A Serotonin Receptor Agonist Ligands

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT2A Serotonin Receptor Agonist Ligands

Unimolecular Fragment Coupling: A New Bond-Forming Methodology via the Deletion of Atom(s)

Introducing Conformational Restraints on 25CN-NBOH: A Selective 5-HT2A Receptor Agonist

Contact Info

Product

Resources

About

Azo Compounds.¹ Oxidation of 1,1-Disubstituted Hydrazines. The Synthesis and Oxidation of cis- and trans-1-Amino-2,6-diphenylpiperidine. A New Stereospecific Ring Closure

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent N-Benzylphenethylamine 5-HT_2A Serotonin Receptor Agonist Ligands

Introducing Conformational Restraints on 25CN-NBOH: A Selective 5-HT_2A Receptor Agonist