Regioselective Opening Research Articles

Synthesis and crystal structure of a chiral lactam and three amino alcohols as potential protein tyrosine phosphates 1B inhibitors

Chiral lactam 2 and three chiral β-amino alcohols 3–5 have been synthesized and characterized by spectroscopic techniques. Regioselective ring opening reaction of chiral styrene oxide by an amine nucleophile was confirmed by X-ray diffraction data. Ligand 2–4 crystallizes in the tetragonal, orthorhombic and tetragonal crystal lattice system respectively. Ligands 2–6 have been used as potential inhibitors for protein tyrosine phosphatase 1B enzyme (PTP1B). The potential inhibitor effect of these molecules to the target protein was investigated by Dock and molecular dynamics calculations. Dock score analysis and Lipinski parameters suggested that ligands 1, 2, 4–6 are potential inhibitors towards PTP1B, thus indicating that the residues Arg24, Arg254 and Met258, Asp29 in the second active site of PTP1B are essential for the high selectivity of inhibitors. The results indicate that the polar hydrogen bonding interacts with Asp29, Gln102, and the amino acid residues of PTP1B are responsible for governing inhibitory potency of ligands 1–6.

Regioselective ring opening of styrene oxide by carbon nucleophiles catalyzed by metal–organic frameworks under solvent-free conditions

In the present study, the regioselective ring opening of styrene oxide by indole, aniline, imidazole, pyrrole and benzimidazole as carbon nucleophiles in the presence of Fe(BTC) (BTC: 1,3,5-benzenetricarboxylate)and Cu3(BTC)2 as heterogeneous solid acid catalysts under solvent-free conditions under mild reaction conditions is reported. Furthermore, Fe(BTC) and Cu3(BTC)2 exhibited higher activity under solvent-free conditions than in the presence of solvents. Control experiments with the corresponding homogeneous catalysts reveal the positive role played by the Lewis acids in these MOFs. On the other hand, the activity of these catalysts is significantly reduced in the presence of pyridine, thus, suggesting the involvement of Lewis acid sites. Both Fe(BTC) and Cu3(BTC)2 MOFs show high regioselectivity in the ring opening of styrene oxide by indole. Fe(BTC) and Cu3(BTC)2 are used for four cycles without significant decay in its activity. In addition, comparison of the fresh and four times used Cu3(BTC)2 catalysts by powder XRD and FT-IR indicate the stability of these catalysts under the present experimental conditions. A suitable mechanism is also proposed based on the observed catalytic data.

Chitosan‐Silica Sulfate Nano Hybrid as a Novel and Highly Proficient Heterogeneous Nano Catalyst for Regioselective Ring Opening of Epoxides via Carboxylic Acids

The synthesis and characterization of chitosan‐silica sulfate nano hybrid (CSSNH) as a novel and efficient heterogeneous nano catalyst involving acid‐base bifunctional activity is described. The catalytic potency and activity of this eco‐friendly catalyst was investigated in regioselective ring opening of epoxides with carboxylic acids to access structurally diverse 1,2‐diol mono‐esters in good to excellent yields. CSSNH catalyst was characterized using different microscopic and spectroscopic techniques encompassing scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, N2 adsorption isotherm, and Fourier transform infrared spectroscopy. The green nature, cheapness, efficiency, ease of preparation, handling and reusability of this new catalyst makes this catalyst to be useful for green industrial processes.

Fluorination of some functionalized cycloalkenes through epoxidation and oxirane opening with Deoxofluor or XtalFluor-E

A convenient, simple synthetic method is described for the synthesis of some fluorinecontaining, highly functionalized cycloalkane derivatives. The synthetic protocol involves the stereoselective epoxidation of selected substituted cyclohexenes as model compounds, followed by regioselective opening of epoxides under various conditions with fluorinating reagents Deoxofluor and XtalFluor-E.

Regioselective Hydrogenolysis of Donor–Acceptor Cyclopropanes with Zn-AcOH Reductive System

A convenient low-cost method for regioselective ring-opening of donor-acceptor cyclopropanes with the Zn-AcOH reductive system was developed. The general character of the method was displayed via efficient reduction of a representative series of 2-(het)arylcyclopropane-1,1-diesters as well as donor-acceptor cyclopropanes with other types of electron-withdrawing activating groups. This method opens a rapid access to γ-substituted propyl-1,1-diesters, ketoesters, cyanoesters, cyanoamides, dinitriles, etc., many of which are not readily accessible with alternative methods. The utility of the synthesized compounds was demonstrated by transforming them into valuable acyclic and cyclic compounds (including pharmacologically relevant carbazoles, δ-lactams, and oxindole derivatives).

A Peerless Aproach: Organophotoredox/Cu(I) Catalyzed, Regioselective, Visible Light Facilitated, Click Synthesis of 1,2,3-Triazoles via Azide–Alkyne [3 + 2] Cycloaddition

A visible light initiated, mild, one pot, multicomponent copper catalyzed azide alkyne [3 + 2] cycloaddition in the presence of organo photoredox catalyst Eosin Y using EtOH:H2O as reaction medium for the synthesis of substituted 1,2,3-triazoles is reported. A facile regioselective ring opening of epoxides followed by 1, 3 dipolar cycloaddition with alkynes under CFL (Compact fluorescent light) irradiation as a source of visible light resulting in the formation of C–N bonds, is the characteristic feature of the present strategy. Scope of the present protocol is further extended by using benzyl chloride in place of epoxide.

Solvent-free synthesis of 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol as potential antiproliferative agents

In this paper is described a synthetic route to 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol, starting from cholesterol and diosgenin, respectively. The products were obtained in two steps by epoxidation followed by aminolysis, through an environmentally friendly and solvent-free method mediated by SZ (sulfated zirconia) as catalyst. The use of SZ allows chemo- and regioselective ring opening of the 5,6α-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by 1H, PENDANT 13C NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the β-aminoalcohols was evaluated on MCF-7 cells after 48h of incubation, by MTT and CVS assays. These methodologies showed that both compounds have antiproliferative activity, being more active the cholesterol analogue. Additionally, the cell images obtained by Harris’ Hematoxylin and Eosin (H&E) staining protocol, evidenced formation of apoptotic bodies due to the presence of the obtained β-aminoalcohols in a dose-dependent manner.

An easy one-step procedure for the synthesis of novel β-functionalised tellurides

Novel β-hydroxy-,β-amino- and β-mercapto- dialkyl- and phenyl-alkyl tellurides have been achieved through regioselective ring opening reactions of oxiranes, aziridines and thiiranes with different Te-nucleophiles, including tellurosilanes. Tellurium-125 NMR chemical shifts of selected compounds have been measured.

Synthesis of (+)‐Patulolide C Using R‐(+)‐γ‐Valerolactone as a Chiral Synthon.

AbstractThe total synthesis of (+)‐Patulolide‐C is accomplished by using enantiopure R‐(+)‐γ‐valerolactone & R‐(+)‐epichlorohydrin as chiral synthons. The strategy adopted for the synthesis is a convergent approach wherein two advanced intermediates were synthesized independently using the chiral synthons and coupled to achieve the skeleton of Patulolide‐C. The important synthetic steps of the synthesis are two carbon homologation of the cyclic lactol, Julia olefination of enone with sulfone in DME, DIBAl‐H mediated regioselective opening of benzylidine acetal, selective oxidation of primary alcohol to aldehyde using BAIB/TEMPO and lactonization of seco‐acid adopting Yamaguchi protocol to afford the macrolide skeleton.

Enantiospecific Total Synthesis of (+)‐3‐epi‐Epohelmin A Using a Nitrogen‐Substituted Donor–Acceptor Cyclopropane

The enantiospecific total synthesis of (+)‐3‐epi‐epohelmin was accomplished by rapid construction of the pyrrolizidine core starting from enantiopure l‐pyroglutamic acid. The key reaction included a highly regio‐ and stereoselective intramolecular cyclopropanation reaction, regioselective ring opening of a nitrogen‐substituted donor–acceptor cyclopropane, stereoselective reduction of a ketone, chemoselective organolithium addition to a Weinreb amide, and chemoselective oxidation of an allylic alcohol.

Enantioselective total synthesis of cis-(+)- and trans-(+)-disparlure

An expedient enantioselective synthetic approach for the gypsy moth sex-attractant pheromone cis-(+)-1 and trans-(+)-disparlure 2 is described employing the optimized combination of organocatalytic MacMillan’s self aldol reaction, Wittig olefination, regioselective ring opening of an epoxide and Mitsunobu esterification reactions as key steps.

Silver‐Catalyzed Atom‐Economic Hydrophosphorylation of Propargyl Epoxides: An Access to 4‐Phosphoryl 2,3‐Allenols and Stereodefined 1‐Phosphoryl 1,3‐Dienes

AbstractThe highly regioselective nucleophilic ring opening of propargyl epoxides by P(O)H compounds based on a silver catalyst is reported. A variety of P(O)H compounds including H‐phosphonates, H‐phosphinates and diarylphosphine oxides can be used to produce 4‐phosphoryl 2,3‐allenols under mild conditions. The stereoselective synthesis of 1‐phosphoryl 1,3‐butadienes from 4‐phosphoryl 2,3‐allenols and organoboronic acids via a palladium‐catalyzed coupling reaction is also described.magnified image

Stereoselective total synthesis of decarestrictine J

Stereoselective total synthesis of decarestrictine J has been accomplished from inexpensive and commercially available starting materials. This concise synthesis utilizes Jacobsen’s hydrolytic kinetic resolution, regioselective ring opening of epoxide, and Yamaguchi macrolactonisation as key steps.

Aziridine-Mediated Ligation at Phenylalanine and Tryptophan Sites.

An efficient approach towards peptide synthesis that allows easy access to variety of small peptides via one-pot aziridine-mediated ligation/desulfurization strategy has been described. The protocol afforded a library of phenylalanine- and tryptophan-containing α-peptides in good yields by regioselective ring-opening of aziridine-3-aryl-2-carboxylates with peptide thioacids, followed by desulfurization.

Syntheses of Tetrahydrobenzoazepinoindoles and Dihydrobenzodiazepinoindoles via Ring-Opening Cyclization of Activated Aziridines with 2-(2-Bromophenyl)-1H-indoles.

Two efficient, modular, step- and pot-economic strategies to access various 5,6,7,12-tetrahydrobenzo[2,3]azepino[4,5-b]indoles and 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[1,7-a]indoles are disclosed that advance via SN2-type regioselective ring opening of enantiopure aziridines with 2-(2-bromophenyl)-1H-indoles at their C3 and indolyl N centers, respectively, followed by Cu-mediated C-N cyclization which furnishes the products in excellent yields with outstanding enantiomeric excesses (up to >99%).

Synthesis and characterization of a novel nanomagnetic phase-transfer catalyst and its application to regioselective synthesis of β-azido and β-nitro alcohols in water

Immobilization of polyethylene glycol-substituted 1-methylimidazolium bromide on the surface of magnetic Fe3O4 nanoparticles through hexane-1,6-diyldicarbamate linker afforded a powerful and reusable heterogeneous phase-transfer catalysis which was successfully used for regioselective ring opening of epoxides with azide and nitrite anions in aqueous medium. The new catalyst can readily be recovered by simple magnetic decantation and recycled several times without appreciable loss of catalytic activity.

A Photocatalyzed Synthesis of Naphthalenes by Using Aniline as a Traceless Directing Group in [4 + 2] Annulation of Amino-benzocyclobutenes with Alkynes

We report a visible-light-promoted synthesis of substituted naphthalenes via [4 + 2] annulation of amino-benzocyclobutenes with alkynes. Amino-benzocyclobutenes, which are conveniently synthesized by [2 + 2] cycloaddition of arynes with ketenes followed by reductive amination, undergo regioselective opening of the cyclobutenyl ring to reveal a presumably distonic radical cation upon photooxidation by an excited iridium complex. The distonic radical cation undergoes the annulation with terminal and internal alkynes as well as diynes to afford structurally diverse naphthalenes. The regiochemistry of the annulation follows the pattern displayed in the addition of nucleophilic carbon radicals to alkynes. The aniline group plays a dual role in which it not only directs the initial photooxidation to generate the amine radical cation but also serves as a leaving group to complete aromatization.

Synthesis of the enantiomers of (3Z,9Z)-cis-6,7-epoxy-3,9-octadecadiene, one of the major components of the sex pheromone of Ectropis oblique Prout

Both enantiomers of (3Z,9Z)-cis-6,7-epoxy-3,9-octadecadiene, one of which is the major component of the sex pheromone of Ectropis oblique Prout, were synthesized in 23% overall yield for the (−)-(6S,7R)-enantiomer and 18% yield for the (+)-(6R,7S)-isomer. This protocol uses a sequential regioselective ring-opening strategy and provides a convenient and reliable access to other structurally related insect sex pheromones. Preliminary biological studies revealed that (−)-(6S,7R)-2a was roughly as active as the natural pheromone, while racemic (±)-2 was less bioactive and (+)-2b was much less bioactive.

Studies towards the total synthesis of cruentaren A and B: Stereoselective synthesis of fragments C1-C11, C12-C22 and C23-C28

Abstract A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn -stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti -stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis -2-butene-1,4-diol respectively.

LiBr/β-CD/IBX/H2O-DMSO: A new approach for one-pot biomimetic regioselective ring opening of chalcone epoxides to bromohydrins and conversion to 1,2,3-triketones

ABSTRACTHighly regioselective ring cleavage of chalcone epoxides to bromohydrins has been carried out in good yields with LiBr in the presence of β-CD using DMSO-H2O as solvent system. The ring-opened product, i.e., bromohydrin, was well adapted to IBX-mediated oxidation in such a fashion that the bromohydrins are transformed to their corresponding 1,2,3-triketones in moderate-to-good yields in one pot.