New synthetic retinoids obtained by palladium-catalyzed tandem cyclisation-hydride capture process

The asymmetric Heck reaction is a powerful method for the synthesis of both tertiary and quaternary chiral carbon centers, with an enantiomeric excess often greater than 80%, and in some cases much higher (up to 99% ee). A variety of carbocyclic and heterocyclic systems can be constructed, including spirocyclic systems. The scope of the reaction with respect to the product alkene isomerization is somewhat limited by problems of regioselectivity, however, these problems are surmountable, and a new generation of ligands that dissociate more rapidly from the products, might improve both enantio-and regiocontrol. A variety of chiral compounds prepared 5.2 N,N Ligands 5.3 P,P Ligands and Derivatives 5.4 Other Types of Ligands and Diastereoselective Reactions 6 Methodological Developments 7 Summary and Conclusions

show abstract

“…[47] A domino asymmetric Heck cyclization-hydride capture process, i.e., asymmetric hydroarylation, of aryl iodide 97 (see also Section 4. …”

Section: Terpenoidsmentioning

confidence: 99%

Asymmetric Heck Reaction

2004

View full text Add to dashboard Cite

show abstract

“…[13] Later on this strategy was implemented to the alkynes as well to access various building blocks leading to natural products. [14,15] Despite some progresses in asymmetric Heck reactions, [16] the advancement in enantioselective version remains challenging, [17] and few protocols have recently been developed by several groups. [18][19][20][21] Tertiary amines, sodium formate have mostly been employed as hydride donors in presence of various metal catalysts and chiral ligands under aqueous condition.…”

Section: Introductionmentioning

confidence: 99%

Reductive Heck Reaction: An Emerging Alternative in Natural Product Synthesis

Ghosh

2019

ChemistrySelect

View full text Add to dashboard Cite

Metal‐catalyzed cross coupling reactions are efficient synthetic methods and developing continuously for the synthesis of diverse range of heterocycles, found in wide range of natural products. Among others, reductive Heck reaction has elegantly been employed to access various natural products. This review article covers the updated summary of relevant literature on the application of reductive Heck reaction for the synthesis of natural products. Discussion on the underlying mechanistic rationale has also been included wherever felt necessary.

show abstract

“…Compounds 10 a (Scheme 1) and 10 b (Scheme 2) were obtained from the corresponding phenols [46,47] by coupling with 3-bromo-2-methylpropene using potassium carbonate in methyl ethyl ketone. The resulting ethers were submitted to a palladium-catalyzed tandem cyclization/Suzuki-coupling reaction to afford benzofuran 11 a , 11 b , and 11 c .…”

Section: Methodsmentioning

confidence: 99%

2,3‐Dihydro‐1‐Benzofuran Derivatives as a Series of Potent Selective Cannabinoid Receptor 2 Agonists: Design, Synthesis, and Binding Mode Prediction through Ligand‐Steered Modeling

Diaz

Phatak

et al. 2009

ChemMedChem

Self Cite

View full text Add to dashboard Cite

We recently discovered and reported a series of N-alkyl-isatin acylhydrazone derivatives that are potent cannabinoid receptor 2 (CB2) agonists. In an effort to improve the druglike properties of these compounds and to better understand and improve the treatment of neuropathic pain, we designed and synthesized a new series of 2,3-dihydro-1-benzofuran derivatives bearing an asymmetric carbon atom that behave as potent selective CB2 agonists. We used a multidisciplinary medicinal chemistry approach with binding mode prediction through ligand-steered modeling. Enantiomer separation and configuration assignment were carried out for the racemic mixture for the most selective compound, MDA7 (compound 18). It appeared that the S enantiomer, compound MDA104 (compound 33), was the active enantiomer. Compounds MDA42 (compound 19) and MDA39 (compound 30) were the most potent at CB2. MDA42 was tested in a model of neuropathic pain and exhibited activity in the same range as that of MDA7. Preliminary ADMET studies for MDA7 were performed and did not reveal any problems.

show abstract

New synthetic retinoids obtained by palladium-catalyzed tandem cyclisation-hydride capture process

Cited by 68 publications

References 31 publications

Asymmetric Heck Reaction

Asymmetric Heck Reaction

Reductive Heck Reaction: An Emerging Alternative in Natural Product Synthesis

2,3‐Dihydro‐1‐Benzofuran Derivatives as a Series of Potent Selective Cannabinoid Receptor 2 Agonists: Design, Synthesis, and Binding Mode Prediction through Ligand‐Steered Modeling

Contact Info

Product

Resources

About