220199-90-6Relevant articles and documents
Direct organocatalytic asymmetric α-hydroxymethylation of ketones and aldehydes
Casas, Jesús,Sundén, Henrik,Córdova, Armando
, p. 6117 - 6119 (2004)
Direct organocatalytic asymmetric α-hydroxymethylation of ketones and aldehydes with formaldehyde has been developed, which furnished the corresponding α-hydroxymethylated adducts with high chemo- and enantioselectivity. The reaction is catalyzed by proline derivatives and is a simple method for the enantioselective synthesis of α-hydroxymethylated ketones and aldehydes, and C-2 symmetric diols.
Structural and catalytic characterization of pichia stipitis OYE 2.6, a useful biocatalyst for asymmetric alkene reductions
Pompeu, Yuri A.,Sullivan, Bradford,Walton, Adam Z.,Stewart, Jon D.
, p. 1949 - 1960 (2012)
We have probed Pichia stipitis CBS 6054 Old Yellow Enzyme 2.6 (OYE 2.6) by several strategies including X-ray crystallography, ligand binding and catalytic assays using the wild-type as well as libraries of site-saturation mutants. The alkene reductase crystallized in space group P 63 2 2 with unit cell dimensions of 127.1×123.4 A and its structure was solved to 1.5 A resolution by molecular replacement. The protein environment surrounding the flavin mononucleotide (FMN) cofactor was very similar to those of other OYE superfamily members; however, differences in the putative substrate binding site were also observed. Substrate analog complexes were analyzed by both UV-Vis titration and X-ray crystallography to provide information on possible substrate binding interactions. In addition, four active site residues were targeted for site saturation mutagenesis (Thr 35, Ile 113, His 188, His 191) and each library was tested against three representative Baylis-Hillman adducts. Thr 35 could be replaced by Ser with no change in activity; other amino acids (Ala, Cys, Leu, Met, Gln and Val) resulted in diminished catalytic efficiency. The Ile 113 replacement library yielded a range of catalytic activities, but had very little impact on stereoselectivity. Finally, the two His residues (188 and 191) were essentially intolerant of substitutions with the exception of the His 191 Asn mutant, which did show significant catalytic ability. Structural comparisons between OYE 2.6 and Saccharomyces pastorianus OYE1 suggest that the key interactions between the substrate hydroxymethyl groups and the side-chain of Thr 35 and/or Tyr 78 play an important role in making OYE 2.6 an (S)-selective alkene reductase. Copyright
Organocatalytic α-hydroxymethylation of cyclopentanone with aqueous formaldehyde: Easy access to chiral δ-lactones
Mase, Nobuyuki,Inoue, Azusa,Nishio, Masaki,Takabe, Kunihiko
, p. 3955 - 3958 (2009)
Optically active lactones are important synthons in perfume and aroma manufacturing. Therefore, developments of efficient asymmetric syntheses are desired. Organocatalytic asymmetric α-hydroxymethylations of cyclopentanone with aqueous formaldehyde have b
A Stereoconvergent Tsuji–Trost Reaction in the Synthesis of Cyclohexenyl Nucleosides
Chino, Marco,D'Alonzo, Daniele,De Fenza, Maria,Esposito, Anna,Guaragna, Annalisa,Palumbo, Giovanni,Talarico, Giovanni,di Giovanni, Concetta
, (2020/02/20)
A highly regio- and stereoselective route to d- and l-cyclohexenyl nucleosides has been devised, using the Tsuji–Trost reaction as the key step. Contrarily to the widely accepted mechanism (involving a net retention of configuration), the reaction proceeded in a highly stereoconvergent manner, providing cis nucleosides regardless of the relative configuration of the starting materials. DFT calculations confirmed the experimental data while suggesting the origin of the stereochemical reaction outcome.
Investigating: Saccharomyces cerevisiae alkene reductase OYE 3 by substrate profiling, X-ray crystallography and computational methods
Powell, Robert W.,Buteler, M. Pilar,Lenka, Sunidhi,Crotti, Michele,Santangelo, Sara,Burg, Matthew J.,Bruner, Steven,Brenna, Elisabetta,Roitberg, Adrian E.,Stewart, Jon D.
, p. 5003 - 5016 (2018/10/17)
Saccharomyces cerevisiae OYE 3 shares 80% sequence identity with the well-studied Saccharomyces pastorianus OYE 1; however, wild-type OYE 3 shows different stereoselectivities toward some alkene substrates. Site-saturation mutagenesis of Trp 116 in OYE 3 followed by substrate profiling showed that the mutations had relatively little effect, opposite to that observed previously for OYE 1. The X-ray crystal structures of unliganded and phenol-bound OYE 3 were solved to 1.8 and 1.9 ? resolution, respectively. Both structures were nearly identical to that of OYE 1, with only a single amino acid difference in the active site region (Ser 296 versus Phe 296, part of loop 6). Despite their essentially identical static X-ray structures, molecular dynamics (MD) simulations revealed that loop 6 conformations differed significantly in solution between OYE 3 and OYE 1. In OYE 3, loop 6 remained nearly as open as observed in the crystal structure; by contrast, loop 6 closed over the active site of OYE 1 by ca. 4 ?. Loop closure likely generates a greater number of active site protein contacts for substrate bound to OYE 1 as compared to OYE 3. These differences provide an explanation for the differing stereoselectivities of OYE 3 and OYE 1, despite their nearly identical X-ray crystal structures.
Toward the total synthesis of klaivanolide: Complete reinterpretation of its originally assigned structure
Ferrié, Laurent,Ferhi, Sabrina,Bernadat, Guillaume,Figadère, Bruno
, p. 6183 - 6189 (2015/03/30)
Klaivanolide is an antiparasitic natural product isolated from Uvaria klaineana, whose structure was originally assigned as a seven-membered lactone ring. Attempts towards the total synthesis of klaivanolide led us to revise its original structural assignment based on both experimental evidence and spectroscopic data. The isolated compound was revealed to be a known molecule, acetylmelodorinol, originally isolated from Melodorum fruticosum. Vibrational circular dichroism simulation of the reassigned structure was also performed to reinvestigate our previous studies on the determination of the absolute configuration of klaivanolide.
Chitosan aerogel beads as a heterogeneous organocatalyst for the asymmetric aldol reaction in the presence of water: An assessment of the effect of additives
Gioia, Claudio,Ricci, Alfredo,Bernardi, Luca,Bourahla, Khadidja,Tanchoux, Nathalie,Robitzer, Mike,Quignard, Francoise
, p. 588 - 594 (2013/02/26)
The catalytic properties of chitosan aerogel for the direct asymmetric aldol reaction in water assisted by various surfactants and acid co-catalysts have been evaluated by employing a range of donor and acceptor systems. A beneficial effect on both the yi
Direct asymmetric aldol reactions inspired by two types of natural aldolases: Water-compatible organocatalysts and ZnII complexes
Paradowska, Joanna,Pasternak, Monika,Gut, Bartosz,Gryzlo, Beata,Mlynarski, Jacek
scheme or table, p. 173 - 187 (2012/02/04)
In this article the utility of water-compatible amino-acid-based catalysts was explored in the development of diastereo- and enantioselective direct aldol reactions of a broad range of substrates. Chiral C2-symmetrical proline- and valine-based
Evaluation of synthetic FK506 analogues as ligands for the FK506-binding proteins 51 and 52
Gopalakrishnan, Ranganath,Kozany, Christian,Gaali, Steffen,Kress, Christoph,Hoogeland, Bastiaan,Bracher, Andreas,Hausch, Felix
scheme or table, p. 4114 - 4122 (2012/06/30)
The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified α-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.
Direct asymmetric α-hydroxymethylation of ketones in homogeneous aqueous solvents
Pasternak, Monika,Paradowska, Joanna,Rogozińska, Maria,Mlynarski, Jacek
scheme or table, p. 4088 - 4090 (2010/08/19)
A chiral prolinamide-based zinc complex promotes the aldol reaction of ketones with aqueous formaldehyde, giving the corresponding adducts in good yields and high ees. The efficient direct aldol reaction of formaldehyde with ketones in homogeneous aqueous
