14 research outputs found
Site selective C–H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy
Mitragynine (MG) is an indole alkaloid from kratom plant that binds opioid receptors and as such presents a scaffold for the development of atypical opioid receptor modulators. Here, the authors report a synthetic method for selective functionalization of the C11 position of MG, and show that this position is essential for fine-tuning opioid receptor signaling efficacy
Substituted Diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes as Stable Caged Proton Sponges
Herein, we report a molecular framework design differing
significantly
from the traditional topology of proton sponges. We developed a synthetic
approach to the preparation of caged secondary amines by acid-catalyzed
rearrangement of fused tetracyclic heterocycles synthesized by intramolecular
criss-cross cycloaddition. Alkylation of amines led to air nonsensitive
diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes (DTDs)
with rare alicyclic scaffolding in high overall yields. Their p<i>K</i><sub>BH</sub>+ values were determined by transprotonation
experiments as well as their sensitivity toward nucleophiles, acids
and bases. Crystal structures of free base and monoprotonated form
are discussed
Substituted Diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes as Stable Caged Proton Sponges
Herein, we report a molecular framework design differing
significantly
from the traditional topology of proton sponges. We developed a synthetic
approach to the preparation of caged secondary amines by acid-catalyzed
rearrangement of fused tetracyclic heterocycles synthesized by intramolecular
criss-cross cycloaddition. Alkylation of amines led to air nonsensitive
diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes (DTDs)
with rare alicyclic scaffolding in high overall yields. Their p<i>K</i><sub>BH</sub>+ values were determined by transprotonation
experiments as well as their sensitivity toward nucleophiles, acids
and bases. Crystal structures of free base and monoprotonated form
are discussed
Substituted Diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes as Stable Caged Proton Sponges
Herein, we report a molecular framework design differing
significantly
from the traditional topology of proton sponges. We developed a synthetic
approach to the preparation of caged secondary amines by acid-catalyzed
rearrangement of fused tetracyclic heterocycles synthesized by intramolecular
criss-cross cycloaddition. Alkylation of amines led to air nonsensitive
diazatetracyclo[4.4.0.1<sup>3,10</sup>.1<sup>5,8</sup>]dodecanes (DTDs)
with rare alicyclic scaffolding in high overall yields. Their p<i>K</i><sub>BH</sub>+ values were determined by transprotonation
experiments as well as their sensitivity toward nucleophiles, acids
and bases. Crystal structures of free base and monoprotonated form
are discussed
Unexpected Heterocyclic Products from Cycloaddition Reactions of Nonsymmetrical Allenyl Aldoketazines with Substituted Alkynes
International audienc
Combined intra-intermolecular criss-cross cycloaddition reactions leading to perfluoroalkylated fused tricyclic nitrogen heterocycles
International audiencePerfluoroalkylated hydrazones 1a–ewere preparedfrom diethyl hydrazinophosphate andwere engaged in the reaction with 3-substitutedhomoallenyl aldehydes according to Zwierzak’smethod. The resulting non-symmetrical perfluoroalkyl-derived azines reacted in combined intra-intermolecular criss-cross cycloaddition with phenyl isocyanate, phenyl isothiocyanate and dimethyl acetylenedicarboxylate producing fused tricyclic heterocycles. Besides, the thermal cyclization of perfluoroalkylated non- symmetrical azines, without added dipolarophile, was carried out providing fused bicyclic systems