83861-75-0Relevant articles and documents
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.
Catalytic Enantioselective Dihalogenation and the Selective Synthesis of (-)-Deschloromytilipin A and (-)-Danicalipin A
Landry, Matthew L.,Hu, Dennis X.,McKenna, Grace M.,Burns, Noah Z.
supporting information, p. 5150 - 5158 (2016/05/19)
A titanium-based catalytic enantioselective dichlorination of simple allylic alcohols is described. This dichlorination reaction provides stereoselective access to all common dichloroalcohol building blocks used in syntheses of chlorosulfolipid natural products. An enantioselective synthesis of ent-(-)-deschloromytilipin A and a concise, eight-step synthesis of ent-(-)-danicalipin A are executed and employ the dichlorination reaction as the first step. Extension of this system to enantioselective dibromination and its use in the synthesis of pentabromide stereoarrays relevant to bromosulfolipids is reported. The described dichlorination and dibromination reactions are capable of exerting diastereocontrol in complex settings allowing X-ray crystal structure analysis of natural and unnatural diastereomers of polyhalogenated stereohexads.
Pheromone Bouquet of the Dried Bean Beetle, Acanthoscelides obtectus (Col.: Chrysomelidae), Now Complete
Vuts, J?zsef,Francke, Wittko,Mori, Kenji,Zarbin, Paulo H. G.,Hooper, Antony M.,Millar, Jocelyn G.,Pickett, John A.,T?th, Mikl?s,Chamberlain, Keith,Caulfield, John C.,Woodcock, Christine M.,Tr?ger, Armin G.,Csonka, éva Bálintné,Birkett, Michael A.
, p. 4843 - 4846 (2015/08/03)
Male-specific volatile components, released by the dried bean beetle, Acanthoscelides obtectus, were identified as methyl (E,R)-2,4,5-tetradecatrienoate, methyl (2E,4Z,7Z)-2,4,7-decatrienoate, methyl (2E,4Z)-2,4-decadienoate, octadecanal and the sesquiterpenes (3Z,6E)- and (3E,6E)-α-farnesene. In olfactometer bioassays, pure methyl (E,R)-2,4,5-tetradecatrienoate was only weakly attractive to unmated females. However, a blend of the six identified compounds released in physiologically relevant ratios and doses proved to be as active as headspace odours collected from live males.
