Academic literature on the topic 'Enantiopure Products - Synthesis'

AbstractDynamic kinetic resolutions of racemic compounds provide elegant synthetic possibilities for the preparation of valuable enantiopure organic molecules with a theoretical maximum 100% yield. This chapter describes the combination of stereoselective enzymatic methods with suitable conditions for the racemization of the slow-reacting enantiomer from racemates of various types of compounds, such as alcohols, amines, and amino acids, for the synthesis of biologically active compounds and natural products. This contribution has been divided into three main topics based on the enzyme that catalyzes the asymmetric transformation and the racemization conditions of choice. These are: (i) the use of hydrolases and metal species; (ii) the use of hydrolases without requiring a metal catalyst for the racemization step; (iii) the use of other enzyme classes. A selection of scalable experimental procedures is provided in each case to demonstrate the robustness of the methodology described.

Haifeng Du at the Chinese Academy of Sciences reported (J. Am. Chem. Soc. 2013, 135, 6810) the borane-catalyzed asymmetric hydrogenation of imine 1 to 2 using the diene 3 as a chiral ligand for boron. A single-enzyme cascade for the reductive transam­ination of acetophenone 4 with amine 5 to produce enantiopure sec-phenethylamine 6 was developed (Chem. Commun. 2013, 49, 161) by Per Berglund at the KTH Royal Institute of Technology in Sweden. A group at Boehringer Ingelheim in Ridgefield, Connecticut, led by Jonathan T. Reeves, disclosed (J. Am. Chem. Soc. 2013, 135, 5565) a procedure for the addition of DMF anion to N-sulfinyl imine 7 to furnish tert-leucine amide 8 with high diastereoselectivity. The tertiary carbinamine 10 was synthesized (Org. Lett. 2013, 15, 34) via the carbolithiation/rearrangement of vinyl­urea 9 as reported by Jonathan Clayden at the University of Manchester. Gregory C. Fu at Caltech reported (Angew. Chem. Int. Ed. 2013, 52, 2525) that the chiral phosphine 12 catalyzed the enantioselective addition of trifluoroacetamide to allene 11 to produce γ-amino ester 13 in enantioenriched form. Adeline Vallribera at the Autonomous University of Barcelona found (Org. Lett. 2013, 15, 1448) that a euro­pium pybox complex effected the highly enantioselective α-amination of β-ketoester 14 to generate 15 on the way to the Parkinson’s disease co-drug L-carbidopa. Hisashi Yamamoto at the University of Chicago and Chubu University reported (J. Am. Chem. Soc. 2013, 135, 3411) that a halfnium(IV) complex of the bishydroxamic acid 17 catalyzed the enantioselective epoxidation of the tertiary homoallylic alcohol 16 to 18. The rearrangement of the allylic carbonate 19 to produce allyl ether 21 with high ee under iridium catalysis in the presence of ligand 20 was disclosed (Org. Lett. 2013, 15, 512) by Hyunsoo Han at the University of Texas, San Antonio. The asymmetric vinylogous aldol reaction of 3-methyl-2-cyclohexen-1-one 22 and α-keto ester 23 to furnish tertiary carbinol 25 using the bifunctional catalyst 24 was developed (Org. Lett. 2013, 15, 220) by Paolo Melchiorre at ICREA and ICIQ in Spain.

The enantioselective bromocyclization of dicarbonyl 1 to form dihydrofuran 3 using thiocarbamate catalyst 2 was developed (Angew. Chem. Int. Ed. 2013, 52, 8597) by Ying-Yeung Yeung at the National University of Singapore. Access to dihydrofuran 5 from the cyclic boronic acid 4 and salicylaldehyde via a morpholine-mediated Petasis borono-Mannich reaction was reported (Org. Lett. 2013, 15, 5944) by Xian-Jin Yang at East China University of Science and Technology and Jun Yang at the Shanghai Institute of Organic Chemistry. Chiral phosphoric acid 7 was shown (Angew. Chem. Int. Ed. 2013, 52, 13593) by Jianwei Sun at the Hong Kong University of Science and Technology to catalyze the enantioselective acetalization of diol 6 to form tetrahydrofuran 8 with high stereoselectivity. Jan Deska at the University of Cologne reported (Org. Lett. 2013, 15, 5998) the conversion of glutarate ether 9 to enantiopure tetrahy­drofuranone 10 by way of an enzymatic desymmetrization/oxonium ylide rearrange­ment sequence. Perali Ramu Sridhar at the University of Hyderabad demonstrated (Org. Lett. 2013, 15, 4474) the ring-contraction of spirocyclopropane tetrahydropyran 11 to produce tetrahydrofuran 12. Michael A. Kerr at the University of Western Ontario reported (Org. Lett. 2013, 15, 4838) that cyclopropane hemimalonate 13 underwent conver­sion to vinylbutanolide 14 in the presence of LiCl and Me₃N•HCl under microwave irradiation. Eric M. Ferreira at Colorado State University developed (J. Am. Chem. Soc. 2013, 135, 17266) the platinum-catalyzed bisheterocyclization of alkyne diol 15 to fur­nish the bisheterocycle 16. Chiral sulfur ylides such as 17, which can be synthesized easily and cheaply, were shown (J. Am. Chem. Soc. 2013, 135, 11951) by Eoghan M. McGarrigle at the University of Bristol and University College Dublin and Varinder K. Aggarwal at the University of Bristol to stereoselectively epoxidize a variety of alde­hydes, as exemplified by 18. The amine 20-catalyzed tandem heteroconjugate addition/Michael reaction of quinol 19 and cinnamaldehyde to produce bicycle 21 with very high ee was reported (Chem. Sci. 2013, 4, 2828) by Jeffrey S. Johnson at the University of North Carolina, Chapel Hill. Quinol ether 22 underwent facile photorearrangement–cycloaddition to 23 under irradiation, as reported (J. Am. Chem. Soc. 2013, 135, 17978) by John A. Porco, Jr. at Boston University and Corey R. J. Stephenson, now at the University of Michigan.

Lipases are a multipurpose enzyme that holds a significant position in industrial applications due to its ability to catalyse a large number of reactions such as hydrolysis, esterification, interesterification, transesterification which makes it a potential candidate. It is also used for the separation of chiral drugs from the racemic mixture and this property of lipase is considered very important in pharmaceutical industries for the synthesis of enantiopure bioactive molecules. Assuming the tremendous importance of lipases, as stereoselective biocatalysts, in pharmaceuticals and various othe