100324-81-0Relevant articles and documents
Boron-Catalyzed Regioselective Deoxygenation of Terminal 1,2-Diols to 2-Alkanols Enabled by the Strategic Formation of a Cyclic Siloxane Intermediate
Drosos, Nikolaos,Morandi, Bill
, p. 8814 - 8818 (2015)
The selective deoxygenation of polyols is a frontier in our ability to harness the stereochemical and structural complexity of natural and synthetic feedstocks. Herein, we describe a highly active and selective boron-based catalytic system for the selective deoxygenation of terminal 1,2-diols at the primary position, a process that is enabled by the transient formation of a cyclic siloxane. The method provides an ideal complement to well-known catalytic asymmetric reactions to prepare synthetically challenging chiral 2-alkanols in nearly perfect enantiomeric excess, as illustrated in a short synthesis of the anti-inflammatory drug (R)-lisofylline. Pick the right one! A highly active and selective boron-based catalytic system enables the selective deoxygenation of terminal 1,2-diols at the primary position via the transient formation of a cyclic siloxane. The utility of this method for the preparation of synthetically challenging chiral 2-alkanols was illustrated by a short synthesis of the anti-inflammatory drug (R)-lisofylline.
Chemoenzymatic enantioselective and stereo-convergent syntheses of lisofylline enantiomers via lipase-catalyzed kinetic resolution and optical inversion approach
Borowiecki, Pawe?,Zdun, Beata,Dranka, Maciej
, (2021/02/27)
Highly enantioselective enzymatic kinetic resolution (EKR) of racemic lisofylline is presented for the first time. A comprehensive optimization of the key parameters of lipase-catalyzed transesterification of racemic lisofylline revealed that optimal biocatalytic system consisted of immobilized lipase type B from Candida antarctica (Chirazyme L-2, C-3) suspended in a mixture of 3 equiv of vinyl acetate as an acetyl donor and ethyl acetate as a solvent. Under optimal reaction conditions, the 1 g-scale (Chirazyme L-2, C-3)-catalyzed kinetic resolution of racemic lisofylline furnished both the EKR products in a homochiral form (>99 % ee) with the 50 % conv., and the highest possible enantioselectivity. The best results in terms of the reaction yields (47–50 %) and enantiomeric purity of the kinetically-resolved optically active products were achieved when the preparative-scale EKR was carried out for 2 h at 60 °C. In addition, stereoinversion of the less biologically-relevant (S)-lisofylline into its (R)-enantiomer was successfully achieved via acetolysis of the respective optically pure (S)-mesylate by using 2 equiv of ceasium acetate and catalytic amount of 18-Crown-6 in dry toluene, followed by K2CO3-mediated methanolysis of (R)-acetate. The elaborated EKR methodology together with enantioconvergent strategy provided a useful chemoenzymatic protocol for the synthesis of complementary enantiomers of titled API. Moreover, we report on the first single-crystal X-ray diffraction (XRD) analyses performed for the synthesized lisofylline enantiomers. Insight into the source of CAL-B stereoselectivity toward racemic lisofylline was gained by molecular docking experiments. In silico theoretical predictions matched very well with experimental results.
Role of Chain Length and Degree of Unsaturation of Fatty Acids in the Physicochemical and Pharmacological Behavior of Drug-Fatty Acid Conjugates in Diabetes
Chitkara, Deepak,Italiya, Kishan S.,Mittal, Anupama,Narisepalli, Saibhargav,Singh, Arihant Kumar
, p. 14217 - 14229 (2021/10/20)
Several drug-fatty acid (FA) prodrugs have been reported to exhibit desirable physicochemical and pharmacological profile; however, comparative beneficial effects rendered by different FAs have not been explored. In the present study, four different FAs (linoleic acid, oleic acid, palmitic acid, and α-lipoic acid) were selected based on their chain length and degree of unsaturation and conjugated to Lisofylline (LSF), an antidiabetic molecule to obtain different drug-FA prodrugs and characterized for molecular weight, hydrophobicity, purity, self-assembly, and efficacy in vitro and in vivo in type 1 diabetes model. Prodrugs demonstrated a 2- to 6-fold increase in the plasma half-life of LSF. Diabetic animals treated with prodrugs, once daily for 5 weeks, maintained a steady fasting blood glucose level with a significant increase in insulin level, considerable restoration of biochemical parameters, and preserved β-cells integrity. Among the different LSF-FA prodrugs, LSF-OA and LSF-PA demonstrated the most favorable physicochemical, systemic pharmacokinetic, and pharmacodynamic profiles.
Efficient Transfer Hydrogenation of Ketones using Methanol as Liquid Organic Hydrogen Carrier
Garg, Nidhi,Paira, Soumen,Sundararaju, Basker
, p. 3472 - 3476 (2020/05/29)
Herein, we demonstrate an efficient protocol for transfer hydrogenation of ketones using methanol as practical and useful liquid organic hydrogen carrier (LOHC) under Ir(III) catalysis. Various ketones, including electron-rich/electron-poor aromatic ketones, heteroaromatic and aliphatic ketones, have been efficiently reduced into their corresponding alcohols. Chemoselective reduction of ketones was established in the presence of various other reducible functional groups under mild conditions.
