Bisphosphine-Triggered One-Pot Sequential [3 + 2]/[3 + 2] Annulation of Allenoates with Cyclic Ketimines

An efficient bisphosphine-triggered one-pot sequential [3 + 2]/[3 + 2] annulation of allenoates with cyclic ketimines was developed, in which the product of the first [3 + 2] annulation is the electron-deficient substrate for the second [3 + 2] annulation reaction. The reaction is exceptionally regioselective and diastereoselective. This novel and highly convergent strategy may open up a new viewpoint in utilizing allenoates to prepare <i>N</i>-fused polycyclic compounds

Brine-Stabilized 2,2,2-Trifluorodiazoethane and Its Application in the Synthesis of CF₃–Substituted Cyclopropane α‑Amino Acids

A facile thermodynamic cyclopropanation of trisubstituted olefinic azlactones with a stock solution of CF₃CHN₂ in CH₃CN is realized. This method shows excellent generality, affording a wide range of trifluoromethyl-substituted cyclopropanes bearing azlactone rings in good to high yields and diastereoselectivities. With the products in hand, the trifluoromethyl-substituted cyclopropane α-amino acids and relative peptide derivatives could be readily obtained

Nucleophilic Lewis Base Dependent Addition Reactions of Allenoates with Trifluoromethylated Cyclic Ketimines

A detailed investigation on the different reactivity patterns shown by phosphorus- and nitrogen-containing Lewis base catalysts in the reactions of allenoates with cyclic trifluoromethyl ketimines was accomplished. With PPh₃, [3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields. Under the catalysis of DABCO, [2 + 2] annulations occurred, producing azetidine derivatives in good to high yields. However, in the presence of pyridine, α,α′-disubstituted allenoates were obtained in very high yields via aza-Morita–Baylis–Hillman reactions. These studies provide an opportunity for diverse synthesis of a variety of <i>N</i>-heterocyclic compounds from the same starting materials

Nucleophilic Lewis Base Dependent Addition Reactions of Allenoates with Trifluoromethylated Cyclic Ketimines

A detailed investigation on the different reactivity patterns shown by phosphorus- and nitrogen-containing Lewis base catalysts in the reactions of allenoates with cyclic trifluoromethyl ketimines was accomplished. With PPh₃, [3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields. Under the catalysis of DABCO, [2 + 2] annulations occurred, producing azetidine derivatives in good to high yields. However, in the presence of pyridine, α,α′-disubstituted allenoates were obtained in very high yields via aza-Morita–Baylis–Hillman reactions. These studies provide an opportunity for diverse synthesis of a variety of <i>N</i>-heterocyclic compounds from the same starting materials

Nucleophilic Lewis Base Dependent Addition Reactions of Allenoates with Trifluoromethylated Cyclic Ketimines

A detailed investigation on the different reactivity patterns shown by phosphorus- and nitrogen-containing Lewis base catalysts in the reactions of allenoates with cyclic trifluoromethyl ketimines was accomplished. With PPh₃, [3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields. Under the catalysis of DABCO, [2 + 2] annulations occurred, producing azetidine derivatives in good to high yields. However, in the presence of pyridine, α,α′-disubstituted allenoates were obtained in very high yields via aza-Morita–Baylis–Hillman reactions. These studies provide an opportunity for diverse synthesis of a variety of <i>N</i>-heterocyclic compounds from the same starting materials

Force profiles of imatinib dissociation from imatinib-c-Kit complex.

<p>(A) Force profile of imatinib unbinding along traditional ATP-channel. (B) Force profile of imatinib unbinding along allosteric-pocket-channel. (C) Averaged force profiles of imatinib unbinding along ATP-channel (red) and allosteric-pocket-channel (black).</p

RMSD (root mean square deviation) profiles of key motifs in imatinib-Abl complex during conventional molecular dynamics simulation.

<p>The reference structure from which the RMSD was calculated is the crystal structure 2HYY.</p

Typical three-dimensional structures of protein kinases shown in Cα ribbon fashion.

<p>(A) is for active conformation, and (B) for inactive conformation. Key structural components of the protein are color coded: A-loop in red, helix αC in purple, others in gray. Type I (for the active conformation) and type II (for the inactive conformation) kinase inhibitors are schematically shown in green wire mesh.</p

RMSD (root mean square deviation) profiles of key motifs in imatinib-c-Kit complex during conventional molecular dynamics simulation.

<p>The reference structure from which the RMSD was calculated is the crystal structure 1T46.</p

Energy profiles of van der Waals (vdW) interaction between imatinib and its targeting kinases during dissociation.

<p>(A) vdW interaction of imatinib-c-Kit system. (B) vdW interaction of imatinib-Abl system. The vdW profiles shown in solid line are for the ATP-channel and those shown in dotted line are for the allosteric-pocket-channel.</p