2529-05-7Relevant academic research and scientific papers
Functional-Group-Directed Diastereoselective Hydrogenation of Aromatic Compounds
Ranade, Vidyadhar S.,Consiglio, Giambattista,Prins, Roel
, p. 8862 - 8867 (1999)
Diastereoselective liquid phase hydrogenation of a series of monosubstituted indane and tetralin substrates was studied on supported rhodium catalysts. Predominantly the cis-cis diastereomer, obtained by hydrogenation from the diastereoface opposite the substituent (at the stereogenic center), and the cis-trans diastereomer, obtained by hydrogenation from the diastereoface on the same side as the substituent, were formed. The diastereoselectivity between the two isomers was dependent on the steric repulsion or the electronic attraction of the substituent with the surface of the catalyst. The hydroxyl group did not exhibit a strong attraction (haptophilicity), and the cis-cis diastereomer was obtained as the major product. The amino group exhibited a very high haptophilicity, yielding primarily the cis-trans diastereomer. The diastereoselectivity obtained in the hydrogenation of all the substrates was influenced on addition of bases to the reaction mixture. In the case of alcoholic substrates, the selectivity to the cis-trans diastereomer could be substantially increased with alkaline hydroxide additives.
Insights into the Substrate Promiscuity of Novel Hydroxysteroid Dehydrogenases
Bertuletti, Susanna,Ferrandi, Erica Elisa,Marzorati, Stefano,Vanoni, Marta,Riva, Sergio,Monti, Daniela
, p. 2474 - 2485 (2020/05/06)
Hydroxysteroid dehydrogenases (HSDHs) are valuable biocatalysts for the regio- and stereoselective modification of steroids, bile acids and other steroid derivatives. In this work, we investigated the substrate promiscuity of this highly selective class of enzymes. In order to reach this goal, a preliminary search of HSDH homologues in in-house or public available (meta)genomes was carried out. Eight novel NAD(H)-dependent HSDHs, showing either 7α-, 7β-, or 12α-HSDH activity, and including, for the first time, enzymes from extremophilic microorganisms, were identified, recombinantly produced, and characterized. Among the novel HSDHs, four highly active (up to 92 U mg?1) NAD(H)-dependent 7β-HSDHs showing negligible similarity towards previously described 7β-HSDHs, were discovered. These enzymes, along with previously characterized HSDHs, were tested as biocatalysts for the stereoselective reduction of a panel of substrates including two α-ketoesters of pharmaceutical interest and selected ketones that partially resemble the structural features of steroids. All the reactions were coupled with a suitable cofactor regeneration system. Regarding the α-ketoesters, nearly all of the tested HSDHs showed a good activity toward the selected substrates, yielding the reduced α-hydroxyester with up to 99% conversions and enantiomeric excesses. On the other hand, only the 7β-HSDHs from Collinsella aerofaciens and Clostridium absonum showed appreciable activity toward more complex ketones, i. e., (±)-trans-1-decalone, but with interesting as well as different selectivity. (Figure presented.).
Chemoselective Oxidation of Equatorial Alcohols with N-Ligated λ3-Iodanes
Mikhael, Myriam,Adler, Sophia A.,Wengryniuk, Sarah E.
supporting information, p. 5889 - 5893 (2019/08/26)
The site-selective and chemoselective functionalization of alcohols in complex polyols remains a formidable synthetic challenge. Whereas significant advancements have been made in selective derivatization at the oxygen center, chemoselective oxidation to the corresponding carbonyls is less developed. In cyclic systems, whereas the selective oxidation of axial alcohols is well known, a complementary equatorial selective process has not yet been reported. Herein we report the utility of nitrogen-ligated (bis)cationic λ3-iodanes (N-HVIs) for alcohol oxidation and their unprecedented levels of selectivity for the oxidation of equatorial over axial alcohols. The conditions are mild, and the simple pyridine-ligated reagent (Py-HVI) is readily synthesized from commercial PhI(OAc)2 and can be either isolated or generated in situ. Conformational selectivity is demonstrated in both flexible 1,2-substituted cyclohexanols and rigid polyol scaffolds, providing chemists with a novel tool for chemoselective oxidation.
Alkane oxidation catalysed by a self-folded multi-iron complex
Mettry, Magi,Moehlig, Melissa Padilla,Gill, Adam D.,Hooley, Richard J.
, p. 120 - 128 (2016/11/09)
A preorganised ligand scaffold is capable of coordinating multiple Fe(II) centres to form an electrophilic CH oxidation catalyst. This catalyst oxidises unactivated hydrocarbons including simple, linear alkanes under mild conditions in good yields with selectivity for the oxidation of secondary CH bonds. Control complexes containing a single metal centre are incapable of oxidising unstrained linear hydrocarbons, indicating that participation of multiple centres aids the CH oxidation of challenging substrates.
The Stereoselective Reductions of Ketones to the Most Thermodynamically Stable Alcohols Using Lithium and Hydrated Salts of Common Transition Metals
Kennedy, Nicole,Cohen, Theodore
, p. 8134 - 8141 (2015/09/02)
A simple method is presented for the highly stereoselective reductions of ketones to the most thermodynamically stable alcohols. In this procedure, the ketone is treated with lithium dispersion and either FeCl2·4H2O or CuCl2·2H2O in THF at room temperature. This protocol is applied to a large number and variety of ketones and is both more convenient and efficient than those commonly reported for the diastereoselective reduction of five- and six-membered cyclic ketones.
Polyketide intermediate mimics as probes for revealing cryptic stereochemistry of ketoreductase domains
Li, Yang,Fiers, William D.,Bernard, Steffen M.,Smith, Janet L.,Aldrich, Courtney C.,Fecik, Robert A.
, p. 2914 - 2922 (2015/02/19)
Among natural product families, polyketides have shown the most promise for combinatorial biosynthesis of natural product-like libraries. Though recent research in the area has provided many mechanistic revelations, a basic-level understanding of kinetic and substrate tolerability is still needed before the full potential of combinatorial biosynthesis can be realized. We have developed a novel set of chemical probes for the study of ketoreductase domains of polyketide synthases. This chemical tool-based approach was validated using the ketoreductase of pikromycin module 2 (PikKR2) as a model system. Triketide substrate mimics 12 and 13 were designed to increase stability (incorporating a nonhydrolyzable thioether linkage) and minimize nonessential functionality (truncating the phosphopantetheinyl arm). PikKR2 reduction product identities as well as steady-state kinetic parameters were determined by a combination of LC-MS/MS analysis of synthetic standards and a NADPH consumption assay. The d-hydroxyl product is consistent with bioinformatic analysis and results from a complementary biochemical and molecular biological approach. When compared to widely employed substrates in previous studies, diketide 63 and trans-decalone 64, substrates 12 and 13 showed 2-10 fold lower KM values (2.4 ± 0.8 and 7.8 ± 2.7 mM, respectively), indicating molecular recognition of intermediate-like substrates. Due to an abundance of the nonreducable enol-tautomer, the kcat values were attenuated by as much as 15-336 fold relative to known substrates. This study reveals the high stereoselectivity of PikKR2 in the face of gross substrate permutation, highlighting the utility of a chemical probe-based approach in the study of polyketide ketoreductases.
An iron catalyst for oxidation of alkyl C-H bonds showing enhanced selectivity for methylenic sites
Prat, Irene,Gomez, Laura,Canta, Merce,Ribas, Xavi,Costas, Miquel
supporting information, p. 1908 - 1913 (2013/03/14)
Many are called but few are chosen: A nonheme iron complex catalyzes the oxidation of alkyl C-H bonds by using H2O2 as the oxidant, showing an enhanced selectivity for secondary over tertiary C-H bonds (see scheme). Copyright
Efficient stereo- and regioselective hydroxylation of alkanes catalysed by a bulky polyoxometalate
Kamata, Keigo,Yonehara, Kazuhiro,Nakagawa, Yoshinao,Uehara, Kazuhiro,Mizuno, Noritaka
scheme or table, p. 478 - 483 (2010/09/17)
Direct functionalization of alkanes by oxidation of C-H bonds to form alcohols under mild conditions is a challenge for synthetic chemistry. Most alkanes contain a large number of C-H bonds that present difficulties for selectivity, and the oxidants employed often result in overoxidation. Here we describe a divanadium-substituted phosphotungstate that catalyses the stereo- and regioselective hydroxylation of alkanes with hydrogen peroxide as the sole oxidant. Both cyclic and acyclic alkanes were oxidized to form alcohols with greater than 96% selectivity. The bulky polyoxometalate framework of the catalyst results in an unusual selectivity that can lead to the oxidation of secondary rather than the weaker tertiary C-H bonds. The catalyst also avoids wasteful decomposition of the stoichiometric oxidant, which can result in the production of hydroxyl radicals and lead to non-selective oxidation and overoxidation of the desired products.
Self-terminating radical cyclizations: How are thiyl radicals performing?
Tan, Kristine J.,White, Jonathan M.,Wille, Uta
supporting information; experimental part, p. 4902 - 4911 (2010/11/05)
The performance of thiyl radicals RS' in "self-terminating radical cyclisations" was explored. Using the medium-sized cyclodecyne (1) as model system, the reaction of PhS' generated by photolysis of (PhS)2 was used to study the intermolecular S-radical addition and subsequent intramolecular radical translocations. This reaction resulted in the formation of three stereoisomeric sulfides 17a in very good yield, which all possess the bicyclo[4.4.0]decane framework with either cis and trans ring fusion. The isomeric bicyclo[5.3,0]decane framework was not: formed. Product identification was performed using a combination of techniques, e.g. synthesis of authentic samples, X-ray analysis and computational studies of the potential energy surface, which also revealed valuable insight into the mechanism, of this radical cyclisation cascade. The (PhS)2/PhS' system provides an efficient source for in situ generated thiols, which mediate reduction of the α-thio radical, e.g., 13a→17a. The radical cascade initiated by the addition of BnS', tBuS' or AllylS', respectively, to cycloalkyne 1 was typically terminated also by reduction, even in the absence of an apparent H-donor, and resulted in formation of various bicyclic and monocyclic thioethers. The desired "selftermination", e.g., β-fragmentation of the S-R bond in radical intermediate 12/13 and release of a stabilized radical R', was only observed, as minor reaction, pathway in one particular instance where tBuS' was generated by autoxidation of tBuSH. Computional studies showed that the different stereochemical outcome of the radical cyclizations involving S-radicals, compared to O- or N-centred radicals, could be attributed to the reversibility of the initial intermolecular Sradical addition to the C≡C triple bond in cycloalkyne 1.
Hydrogen-transfer reduction of carbonyl compounds catalysed by nickel nanoparticles
Alonso, Francisco,Riente, Paola,Yus, Miguel
, p. 1939 - 1942 (2008/09/19)
We report for the first time the hydrogen-transfer reduction of carbonyl compounds catalysed by well-defined nickel(0) nanoparticles. The nickel nanoparticles could be reutilised several times in a very simple reaction medium composed of the nickel nanoparticles, isopropanol and the substrate, without any added base.
