Stereoselective Synthesis of (<i>E</i>)-2-En-4-ynoic Acids with Ynolates: Catalytic Conversion to Tetronic Acids and 2-Pyrones

A highly torquoselective olefination of alkynoates to provide functionalized tetrasubstituted olefins, (E)-2-en-4-ynoic acids, is described. Addition of Brønsted acids dramatically switched the mode of the Ag(I)-catalyzed cyclization of the resulting enyne carboxylic acids to give either tetronic acids or 2-pyrones

The Effect of Alkynyl Groups on Torquoselectivity. Highly Stereoselective Olefination of Alkynyl Ketones with Ynolates

The Effect of Alkynyl Groups on Torquoselectivity. Highly Stereoselective Olefination of Alkynyl Ketones with Ynolate

The Effect of Alkynyl Groups on Torquoselectivity. Highly Stereoselective Olefination of Alkynyl Ketones with Ynolates

The Effect of Alkynyl Groups on Torquoselectivity. Highly Stereoselective Olefination of Alkynyl Ketones with Ynolate

Stereoselective Olefination of Unfunctionalized Ketones via Ynolates

Ynolates react with ketones at room temperature to afford α,β,β-trisubstituted acrylates (tetrasubstituted olefins) with 2:1−8:1 geometrical selectivities. This can be regarded as a new olefination reaction of ketones giving tetrasubstituted olefins in good yield, even in the case of sterically hindered substrates. The reaction mechanism involves cycloaddition of ynolates with a carbonyl group and subsequent thermal electrocyclic ring-opening of the resulting β-lactone enolates. The stereoselectivity is determined in the ring-opening, which is regulated by torquoselectivity. In this paper, we describe the scope and limitations of olefination of ketones via ynolates and discuss the stereocontrol mechanism

Total Synthesis of (+)- and (−)-Sundiversifolide via Intramolecular Acylation and Determination of the Absolute Configuration

Intramolecular acylation of an organolithium leads to an efficient stereocontrolled total synthesis of both enantiomers of sundiversifolide. The absolute configuration was determined by HPLC analysis and allelopathy assay. The γ-lactone moiety resulted from a butenolide was obtained by the condensation of a bicyclic α-hydroxyhemiacetal with Ph3PCMe(CO2R)

Synthesis of Multisubstituted Furans, Pyrroles, and Thiophenes via Ynolates

An efficient synthetic method for the preparation of multisubstituted furans, thiophenes, and pyrroles using ynolates was developed. This novel formal [4 + 1] annulation by C2−C3 and C3−C4 bond formations includes cycloaddition, cyclization, decarboxylation, and dehydration as key steps

Synthesis of Multisubstituted Furans, Pyrroles, and Thiophenes via Ynolates

An efficient synthetic method for the preparation of multisubstituted furans, thiophenes, and pyrroles using ynolates was developed. This novel formal [4 + 1] annulation by C2−C3 and C3−C4 bond formations includes cycloaddition, cyclization, decarboxylation, and dehydration as key steps

Synthesis and Structure−Affinity Relationships of Novel <i>N</i>-(1-Ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with Potent Serotonin 5-HT₃ and Dopamine D₂ Receptor Antagonistic Activity

A structurally original series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides derived from the corresponding benzamide 5 were prepared and evaluated for their binding affinity for the dopamine D2 and serotonin 5-HT3 receptors using rat striatum and rat cortical membrane, respectively. Many of the synthesized pyridine-3-carboxamides exhibited nanomolar binding affinity for the serotonin 5-HT3 receptor along with moderate to high binding affinity for the dopamine D2 receptor. Introduction of the more lipophilic bromine atom and methylamino group at the 5- and 6-positions of the pyridine ring, respectively, enhanced the affinity for the dopamine D2 receptor while keeping a potent serotonin 5-HT3 receptor binding affinity. As a result of structure−affinity relationships, the 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxamide 53 was selected as the most promising product showing a high binding affinity for both receptors. Compound 53 affinity for the dopamine D2 and serotonin 5-HT3 receptors was much more potent than that of metoclopramide (dopamine D2 receptor; 23.3 nM vs 444 nM, serotonin 5-HT3 receptor; 0.97 nM vs 228 nM). Optical resolution of the racemate 53 brought about a dramatic change in the pharmacological profile with (R)-53 exhibiting a strong affinity for both the dopamine D2 and serotonin 5-HT3 receptors, while the corresponding (S)-53 had a potent serotonin 5-HT3 receptor binding affinity and a moderate dopamine D2 receptor binding affinity. X-ray crystallographic study of (R)-53 revealed the existence of two energically stable conformers just like two mirror images. This may account for (R)-53 high affinity for both the dopamine D2 and serotonin 5-HT3 receptors. Pharmacologically, (R)-53 [AS-8112] showed a potent antagonistic activity for both the dopamine D2 and serotonin 5-HT3 receptors in vivo tests and dose-dependently inhibited both the incidence and frequency of emetic episodes induced by cisplatin (ferrets) and morphine (dogs) with ID50 values of 27.1 μg/kg, po and 136 μg/kg, po, respectively. On the basis of this pharmacological profile, (R)-53 is now under further investigation as a potential broad antiemetic agent

Total Synthesis of (+)- and (−)-Sundiversifolide via Intramolecular Acylation and Determination of the Absolute Configuration

Intramolecular acylation of an organolithium leads to an efficient stereocontrolled total synthesis of both enantiomers of sundiversifolide. The absolute configuration was determined by HPLC analysis and allelopathy assay. The γ-lactone moiety resulted from a butenolide was obtained by the condensation of a bicyclic α-hydroxyhemiacetal with Ph3PCMe(CO2R)

Years of observation of humpback whales which observed in three different breeding areas (Ogasawara, Amami, and Okinawa) in the different years.

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