13949-93-4Relevant articles and documents
Chiral Cyclic Aliphatic Linkers as Building Blocks for Selective Dopamine D2or D3Receptor Agonists
Battiti, Francisco O.,Bonifazi, Alessandro,Katritch, Vsevolod,Newman, Amy Hauck,Zaidi, Saheem A.
supporting information, p. 16088 - 16105 (2021/11/16)
Linkers are emerging as a key component in regulating the pharmacology of bitopic ligands directed toward G-protein coupled receptors (GPCRs). In this study, the role of regio- and stereochemistry in cyclic aliphatic linkers tethering well-characterized primary and secondary pharmacophores targeting dopamine D2 and D3 receptor subtypes (D2R and D3R, respectively) is described. We introduce several potent and selective D2R (rel-trans-16b; D2R Ki = 4.58 nM) and D3R (rel-cis-14a; D3R Ki = 5.72 nM) agonists while modulating subtype selectivity in a stereospecific fashion, transferring D2R selectivity toward D3R via inversion of the stereochemistry around these cyclic aliphatic linkers [e.g., (-)-(1S,2R)-43 and (+)-(1R,2S)-42]. Pharmacological observations were supported with extensive molecular docking studies. Thus, not only is it an innovative approach to modulate the pharmacology of dopaminergic ligands described, but a new class of optically active cyclic linkers are also introduced, which can be used to expand the bitopic drug design approach toward other GPCRs.
Photo/N-Heterocyclic Carbene Co-catalyzed Ring Opening and γ-Alkylation of Cyclopropane Enal
Dai, Lei,Ye, Song
supporting information, p. 986 - 990 (2020/02/28)
An unprecedented photo/NHC-co-catalyzed ring-opening C-C bond cleavage of cyclopropane enal and the following γ-alkylation with a halogenated compound via radicals were established, affording the corresponding γ-alkylated α,β-unsaturated esters in moderate to good yields.
The direct preparation of functionalised cyclopropanes from allylic alcohols or α-hydroxyketones using tandem oxidation processes
McAllister, Graeme D.,Oswald, Magalie F.,Paxton, Richard J.,Raw, Steven A.,Taylor, Richard J.K.
, p. 6681 - 6694 (2007/10/03)
New manganese dioxide-mediated tandem oxidation processes (TOPs) have been developed, which facilitate the direct conversion of allylic alcohols and α-hydroxyketones into polysubstituted functionalised cyclopropanes. In the simplest version, the oxidation of an allylic alcohol is carried out in the presence of a stabilised sulfurane, and the intermediate α,β-unsaturated carbonyl compound undergoes in situ cyclopropanation. By using a combination of stabilised phosphorane and sulfurane, the direct conversion of allylic alcohols or α-hydroxyketones into functionalised cyclopropanes is achieved, with in situ cyclopropanation being followed by Wittig olefination, or vice versa. The application of these methods to a formal synthesis of the lignan (±)-picropodophyllone, and to novel analogues of the insecticide allethrin II, is described.
