190848-36-3Relevant articles and documents
Rapid Optical Determination of Enantiomeric Excess, Diastereomeric Excess, and Total Concentration Using Dynamic-Covalent Assemblies: A Demonstration Using 2-Aminocyclohexanol and Chemometrics
Herrera, Brenden T.,Moor, Sarah R.,McVeigh, Matthew,Roesner, Emily K.,Marini, Federico,Anslyn, Eric V.
supporting information, p. 11151 - 11160 (2019/08/07)
Optical analysis of reaction parameters such as enantiomeric excess (ee), diastereomeric excess (de), and yield are becoming increasingly useful as assays for differing functional groups become available. These assays typically exploit reversible covalent or noncovalent assemblies that impart optical signals, commonly circular dichroism (CD), that are indicative of the stereochemistry and ee at a stereocenter proximal to the functional group of interest. Very few assays have been reported that determine ee and de when two stereocenters are present, and none have targeted two different functional groups that are vicinal and lack chromophores entirely. Using a CD assay that targets chiral secondary alcohols, a separate CD assay for chiral primary amines, a UV-vis assay for de, and a fluorescence assay for concentration, we demonstrate a work-flow for speciation of the enantiomers and diastereomers of 2-Aminocyclohexanol as a test-bed analyte. Because of the fact the functional groups are vicinal, we found that the ee determination at the two stereocenters is influenced by the adjacent center, and this led us to implement a chemometric patterning approach, resulting in a 4% absolute error in full speciation of the four stereoisomers. The procedure presented herein would allow for the total speciation of around 96 reactions in 27 min using a high-Throughput experimentation routine. While 2-Aminocyclohexanol is used to demonstrate the methods, the general workflow should be amenable to analysis of other stereoisomers when two stereocenters are present.
Backbone modification of β-hairpin-forming tetrapeptides in asymmetric acyl transfer reactions
Chen, Peng,Qu, Jin
scheme or table, p. 2994 - 3004 (2011/07/08)
Synthetic oligopeptides as mimics of enzymes have been increasingly exploited as catalysts for asymmetric reactions, but highly effective oligopeptide catalysts with relatively low molecular weight are still in great demand. In this paper, we showed the conformational engineering of the β-hairpin-forming tetrapeptide 4 which was first reported by Miller's group as the catalyst for the asymmetric acyl transfer reaction of trans-2-(N-acetylamino)cyclohexan-1-ol (krel = 28). Through our backbone modification strategy, thioamide and sulfonamide as the isosteres of amide were introduced in the β-hairpin secondary structure. The thioxo peptides also adopt β-hairpin conformations as the oxopeptide supported by the combined use of NMR, IR, and X-ray techniques. Thioxo tetrapeptide 14 formed a more constrained β-hairpin conformation and therefore delivered much higher enantioselectivity (krel = 109) in the same reaction. Moreover, the examination of the conformational changes of tetrapeptide 8 upon the protonation of the Nπ-methylhistidine moiety provided evidence to explain the variation of its catalytic efficiency in the asymmetric acyl-transfer reaction.
Asymmetric acylation reactions catalyzed by conformationally biased octapeptides
Jarvo, Elizabeth R.,Vasbinder, Melissa M.,Miller, Scott J.
, p. 9773 - 9779 (2007/10/03)
Octapeptides capable of adopting β-hairpin conformations have been found to function as efficient catalysts for the kinetic resolution of certain racemic secondary alcohols. Parallel solid phase synthesis of a series of peptides with the common feature of the D-Pro-Gly sequence at the turn region (i+3 to i+4) was carried out to yield a family of octapeptide catalysts. The peptides were then screened for their efficiency in a number of enantioselective acylation reactions. (C) 2000 Elsevier Science Ltd.
