87337-68-6Relevant academic research and scientific papers
Regioselective Epoxidations by Cytochrome P450 3A4 Using a Theobromine Chemical Auxiliary to Predictably Produce N-Protected β- or γ-Amino Epoxides
Polic, Vanja,Cheong, Kin Jack,Hammerer, Fabien,Auclair, Karine
, p. 3983 - 3989 (2017)
N-Protected β- and γ-amino epoxides are useful chiral synthons. We report here that the enzyme cytochrome P450 3A4 can catalyze the formation of such compounds in a regio- and stereoselective manner, even in the presence of multiple double bonds or aromatic substituents. To this end, the theobromine chemical auxiliary is used not only to control the selectivity of the enzyme, but also as a masked amine, and to facilitate product recovery. Theobromine predictably directed epoxidation at the double bond of the fourth carbon from the theobromine group. Unlike with most catalysts, the selectivity did not depend on electronic or steric factors but rather on the position of the olefin relative to the theobromine group. (Figure presented.).
A Systematic Study of Unsaturation in Lipid Nanoparticles Leads to Improved mRNA Transfection In Vivo
Lee, Sang M.,Cheng, Qiang,Yu, Xueliang,Liu, Shuai,Johnson, Lindsay T.,Siegwart, Daniel J.
supporting information, p. 5848 - 5853 (2021/02/05)
Lipid nanoparticles (LNPs) represent the leading concept for mRNA delivery. Unsaturated lipids play important roles in nature with potential for mRNA therapeutics, but are difficult to access through chemical synthesis. To systematically study the role of unsaturation, modular reactions were utilized to access a library of 91 amino lipids, enabled by the synthesis of unsaturated thiols. An ionizable lipid series (4A3) emerged from in vitro and in vivo screening, where the 4A3 core with a citronellol-based (Cit) periphery emerged as best. We studied the interaction between LNPs and a model endosomal membrane where 4A3-Cit demonstrated superior lipid fusion over saturated lipids, suggesting its unsaturated tail promotes endosomal escape. Furthermore, 4A3-Cit significantly improved mRNA delivery efficacy in vivo through Selective ORgan Targeting (SORT), resulting in 18-fold increased protein expression over parent LNPs. These findings provide insight into how lipid unsaturation promotes mRNA delivery and demonstrate how lipid mixing can enhance efficacy.
Studies on the Photochemical Reactions of α,β-Acetylenic Ketones with Tetramethylethylene
Saba, Shahrokh,Wolff, Steven,Schroeder, Clemens,Margaretha, Paul,Agosta, William C.
, p. 6902 - 6907 (2007/10/02)
With exclusion of acid, photolysis of mixtures of 1 and 2 in benzene yields 7a and 8a, which rearrange readily to 3, the previously isolated product.Labeling experiments show that these dienes arise by intramolecular 1,4 transfer of hydrogen.Irradiation o
