Simple Functional Group Research Articles

Highly Enantioselective Synthesis of Chiral Cyclopropyl Nucleosides via Catalytic Asymmetric Intermolecular Cyclopropanation.

An efficient route to construct chiral cyclopropyl purine nucleoside analogues has been established via the catalytic asymmetric Michael-initiated ring-closure reactions of α-purine acrylates with α-bromo-carboxylic esters. Using (DHQD)2AQN as the catalyst, various chiral cyclopropyl purine nucleoside analogues with a chiral quaternary stereocenter were obtained in 72-98% yields, excellent diastereoselectivities, and 93-97% ee. Through simple functional group transformations, diverse chiral cyclopropyl purine nucleosides with hydroxymethyl group or carboxyl group were obtained.

Biocatalytic site- and enantioselective oxidative dearomatization of phenols.

Biocatalytic transformations employed by chemists are often restricted to simple functional group interconversions. In contrast, Nature has developed complexity-generating biocatalytic reactions within natural product pathways. These sophisticated catalysts are rarely employed by chemists as the substrate scope, selectivity and robustness of these catalysts are unknown. Our strategy to bridge the gap between the biosynthesis and synthetic chemistry communities leverages the diversity of catalysts available within natural product pathways. Starting from a suite of biosynthetic enzymes, catalysts with complementary substrate scope as well as selectivity can be identified. This strategy has been applied to the oxidative dearomatization of phenols, a chemical transformation that rapidly builds molecular complexity from simple starting materials and cannot be accomplished with high site- and enantioselectivity using existing catalytic methods. Using enzymes from biosynthetic pathways, we have successfully developed a method to produce ortho-quinol products with controlled site- and stereoselectivity. Further, we have capitalized on the scalability and robustness of this method in gram-scale reactions as well as multi-enzyme and chemoenzymatic cascades.

Pyrene-Based Approach to Tune Emission Color from Blue to Yellow.

The development of functionalized, luminescent, pyrene-based monomers has been and continues to be an area of great interest in terms of the design and fabrication of optical and electronic devices. Herein, a facile strategy to tune the emission color of pyrene-based chromophores has been established by simple functional group modification at the para position to the diphenylamino on the donor building block. Intriguing photophysical properties were obtained and are described both in different solutions and in the solid state. The results obtained could be explained by the Hammett method and by density functional theory (DFT) calculations. A good correlation was observed between the Hammett σpara constants of the functional groups para to the phenyl and the wavenumber (cm-1) of the emission profile. This positive correlation, namely between the σ constants of the functional groups and the emission properties of the monomers, can be used to develop a predictive method for these types of systems.

Synthesis of polyfluorene containing simple functional end group with aryl palladium(II) complexes as initiators

A series of aryl Pd(II) complexes of the formula PdL2(Ar)Br (L = PPh3, 1–8; L = PCy3, 9–11; L = PEt3, 12) and [Pd(P(o-tol)3)(Ar)(μ-Br)]2 (13–18; Ar = substituted phenyl with simple functional group, Cy = cyclohexyl, o-tol = o-tolyl) has been synthesized by direct oxidative addition of Pd(0) precursor and excess aryl bromide. In contrast, the corresponding Pd(II) bromide coordinated with partly aryl-aryl exchanged phosphine was isolated for the bidentate 1,2-bis(diphenylphosphino)ethane (dppe) or 1,3-bis(diphenylphosphino)propane (dppp) ligand, indicating that the aryl-aryl exchange occurs more easily probably because of the chelate effect of the bidentate ligand and the intramolecular π-π interaction between neighboring phenyl rings. Suzuki-Miyaura coupling polymerization of AB-type fluorene monomer with these Pd(II) complexes as initiators was carried out. The aryl Pd(II) complexes with P(o-tol)3 exhibit the catalyst-transfer polymerization at room temperature. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) characterization and end group analysis reveal that the functional group is anchored at the end of polymer backbone. Furthermore, the groups can be transferred to other more useful active groups via simple organic reaction.

Modification of existing antibiotics in the form of precursor prodrugs that can be subsequently activated by nitroreductases of the target pathogen

The use of existing antibiotics in the form of prodrug followed by activation using enzymes of pathogenic origin could be a useful approach for antimicrobial therapy. To investigate this idea, a common antibiotic, sulfamethoxazole has been redesigned in the form of a prodrug by simple functional group replacement. Upon reductive activation by a type I nitroreductase from a pathogen, the drug displayed enhanced antimicrobial capacity. This strategy could improve the efficacy and selectively of antibiotics and reduce the incidence of resistance.

Transition-metal-free synthesis of indole-fused dibenzo[b,f][1,4]oxazepines via Smiles rearrangement.

A one-pot transition-metal-free approach for the synthesis of indole-fused dibenzo[b,f][1,4]oxazepines from 2-(1H-indol-2-yl)phenol and 1,2-dihalobenzenes or 2 halonitroarenes has been developed. The proposed mechanism for this transformation features a Smiles rearrangement favoured over a direct intramolecular nucleophilic cyclization, which affords the corresponding products in different regioselectivities. This reaction also features simple reaction conditions and wide functional group tolerance.

見過ごされていた共役イミンの環化反応：合成的展開と生体機能制御の可能性

Imines are among the most ubiquitous species in organic and bioorganic chemistry; however, the reactivities of N-alkyl unsaturated imines have not been thoroughly explored due to their instability profiles. We describe the novel reactivity of the N-alkyl-unsaturated imines derived from substituted aldehydes, aminoalcohol or diamine, and paraformaldehyde to produce 2,6,9-triazabicyclo [3.3.1] nonanes, 1,5-diazacyclooctanes, hexahydropyrimidines and 1,3,5-triazacyclooctanes through a formal [4+4], [4+2] and [4+2+2] cycloaddition reaction. When using the chiral aminoalcohol, the iminocycloaddition reaction proceeded in a stereocontrolled manner. The reaction products were successfully transformed via simple functional group manipulations to the variously substituted chiral 1,3-diamines, which could not be simply accessed by the other methods. Furthermore, we synthetically demonstrated that eight-membered heterocycles, namely, 2,6,9-triazabicyclo [3.3.1] nonanes and 1,5-diazacyclooctanes, are the exclusive products of the reaction of acrolein with biologically relevant amines, e.g., polyaimes. These compounds are produced in much higher amounts and efficiencies than the acrolein biomarker in current use. Our results not only indicate that eight-membered heterocycles may potentially be used as new biomarkers, but also strongly suggest the involvement of these heterocycles in various important biological phenomena, e.g., an acrolein-mediated mechanism underlying oxidative stress or inhibitory effects of amyloid peptide fibrillization.

Unexplored Reactivity of N-Alkyl Unsaturated Imines: A Simple Procedure for Producing Optically Active 1,3-Diamines via a Stereocontrolled Formal [4+2] and [4+2+2] Iminocycloaddition

Abstract Imines are among the most ubiquitous species in organic and bioorganic chemistry; however, the reactivities of N-alkyl unsaturated imines have not been thoroughly explored due to their instability profiles. Here, we describe the novel reactivity of N-alkyl unsaturated imines derived from substituted aldehydes, a chiral aminoalcohol, and paraformaldehyde to produce hexahydropyrimidines and 1,3,5-triazacyclooctanes through a formal asymmetric [4+2] and [4+2+2] cycloaddition reaction in a stereocontrolled manner. The reaction products were successfully transformed via simple functional group manipulations to the variously substituted chiral 1,3-diamines, which could not be simply accessed by other methods.

ChemInform Abstract: Organotrifluoroborates: Another Branch of the Mighty Oak

AbstractReview: [69 refs.

Application of the functional renormalization group method to classical free energy models

A simple functional renormalization group method is presented to correct the behavior of classical free energy models near the critical point. This approach is applied to the Soave–Redlich–Kwong equation of state to illustrate its ability to better reproduce the phase behavior of simple fluids and to understand the influence of its parameters on the shape of the vapor‐liquid phase diagram. The method is then extended to account for the correlations induced by intramolecular bonds. It is then applied to a first‐order thermodynamic perturbation theory for chain fluids to examine fluids composed of linearly bonded Lennard‐Jones atoms. Unlike previous approaches for applying renormalization group corrections to chain fluids, this is able to accurately reproduce the critical point without predicting an overly flat liquid‐vapor coexistence region. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2985–2992, 2015

Organotrifluoroborates: Another Branch of the Mighty Oak.

Over the past two decades, organotrifluoroborates have evolved from being chemical curiosities to important reagents for the elaboration of organic molecules. Aside from their often-unique reactivity patterns, favorable features of these reagents include their ease of preparation/isolation, reliable crystallinity, enhanced stability, and monomeric structure. Currently >600 structurally diverse reagents of this class are commercially available, and >850 such compounds have been reported from the author's laboratory. The organotrifluoroborates can be utilized as shelf-stable precursors to a variety of end products through simple functional group transformations and have also been employed as partners in cross-coupling reactions between aromatic, alkenyl, alkynyl, and alkyl substrates in library or individual formats. Within the realm of cross-coupling reactions, organotrifluoroborates provide a practical entry to substructural entities not readily accessed using other organometallic reagents, and most recently, the development of a novel mechanistic paradigm for cross-coupling promises to expand the range of accessible cross-coupling partners even further to include both single- and two-electron processes.

Opposite Enantioselectivity in the Bioreduction of (Z)‐β‐Aryl‐β‐cyanoacrylates Mediated by the Tryptophan 116 Mutants of Old Yellow Enzyme 1: Synthetic Approach to (R)‐ and (S)‐β‐Aryl‐γ‐lactams

AbstractThe Trp 116 mutants of Old Yellow Enzyme 1 that catalyse the reduction of (Z)‐β‐aryl‐β‐cyanoacrylates give the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g., alanine) make the substrate bind to the enzyme′s active site in a “classical” orientation, affording the (S)‐enantiomer of the reduced product. When the size of the amino acid increases (e.g., leucine), a “flipped” binding mode is adopted by the substrate, which is converted into the corresponding (R)‐derivative. With bulky amino acids (e.g., tryptophan in the wild‐type) the reduction does not occur. The enantiomerically enriched cyanopropanoates thus prepared can be converted into the corresponding (S)‐ and (R)‐β‐aryl‐γ‐lactams, precursors of inhibitory neurotransmitters belonging to the class of γ‐aminobutyric acids, by a simple functional group interconversion in a sequential one‐pot procedure.magnified image

Aminomaleimide fluorophores: a simple functional group with bright, solvent dependent emission.

Amino-substituted maleimides form a new class of highly emissive compounds, with large Stokes shifts (>100 nm) and high quantum yields (up to ∼60%). Emission is responsive to the maleimide's environment with both a red-shift, and quenching, observed in protic polar solvents. Aminomaleimides are easily functionalised, providing a versatile fluorescent probe.

Designing a Cu(II)-ArCu(II)-ArCu(III)-Cu(I) catalytic cycle: Cu(II)-catalyzed oxidative arene C-H bond azidation with air as an oxidant under ambient conditions.

On the basis of our recent discovery of high valent organocopper compounds, we have designed and achieved efficient copper(II)-catalyzed oxidative arene C-H bond azidation under very mild aerobic conditions by using NaN3 as an azide source. In the presence of a Cu(II) catalyst, a number of azacalix[1]arene[3]pyridines underwent direct arene C-H bond cupration through an electrophilic aromatic metalation pathway to form an arylcopper(II) intermediate. Oxidized by a free copper(II) ion, the arylcopper(II) intermediate was transformed into an arylcopper(III) species that subsequently cross-coupled with azide to furnish the formation of aryl azide products with the release of a copper(I) ion. Under ambient catalytic reaction conditions, the copper(I) species generated was oxidized by air into copper(II), which entered into the next catalytic cycle. Application of the method was demonstrated by the synthesis of functional azacalix[1]arene[3]pyridines by means of simple and practical functional group transformations of azide. The showcase of the Cu(II)-ArCu(II)-ArCu(III)-Cu(I) catalytic cycle would provide a new strategy for the design of copper(II)-catalyzed aerobic oxidative arene C-H bond activation and transformations.

Functional Group-Dependent Self-Assembled Nanostructures from Thermo-Responsive Triblock Copolymers

The ability to control the formation of nanostructures through self-assembly of amphiphilic block copolymers is of great interest in the field of biology and catalysis. In this work we have studied the self-assembling behavior of a new class of thermo-responsive triblock copolymers containing poly(ethylene glycol), and demonstrated the manner in which the aggregation pattern changed on simple functional group transformation on the copolymers. Two different triblock copolymers, poly(ethylene glycol)-b-poly(N-ispropylacrylamide)-b-poly(t-butyl acrylate) (P1) and poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(glycidyl methacrylate) (P2) were synthesized using reversible addition-fragmentation chain transfer (RAFT) technique. It was observed that P1 and P2 displayed different temperature dependent solution properties in water, with P1 forming micelles above the LCST of the PNIPA while P2 showing macroscopic phase separation under similar conditions. Thereafter, the tert-butyl group of P1 was converted to the corresponding acid (P1a) and the epoxy groups of P2 was converted to diols (P2a), thus transforming the hydrophobic blocks to hydrophilic ones. Quite interestingly, such transformations led to significant changes in their self-assembling behavior, as both P1a and P2a were seen to form vesicles beyond the LCST of PNIPA. Changes in the hydrophilic fraction in the block copolymers by subtle changes in the functionality and temperature led to the formation of varied nanostructured assemblies, as evident from dynamic light scattering (DLS), transmisison electron microscopy (TEM), and steady-state fluorescence analysis. Such formation of thermo-responsive vesicles induced by simple structural changes in the copolymers is quite interesting and highly significant in drug delivery applications.

Synthesis of l-azaisotryptophan and its analogs: a general access to new 2-substituted azaindoles

l-(N-Cbz)-7-azaisotryptophan, l-(N-Cbz)-1a, a new isostere of tryptophan, was synthesized by reacting Li2-(N-Boc)-2-amino-3-picoline, Li2-(N-Boc)-2a, with appropriately protected l-aspartic acid followed by simple functional group manipulation. This synthetic success led us to access a set of analogs of azaisotryptophan (4a–c; 6a–c) as well as a new class of chiral amines (7a–c; 8a–c) for future application in asymmetric synthesis and design of homochiral ligands. Further, we have generalized the method substantiating a variety of new azaindol-2-yl derivatives (10aa–10lc) with functionalized substituents. In a preliminary luminescence characterization, l-(N-Cbz)-1a has exhibited about 30nm bathochromic shifted fluorescence emission compared to tryptophan and (N-Cbz)-tryptophan.

Stereodivergent Synthesis of Enantioenriched 4-Hydroxy-2-cyclopentenones

Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of intermediates in chemical synthesis. A route to this class of compound has been developed. Key steps include Noyori reduction (which establishes the stereochemistry of the product), ring-closing metathesis, and simple functional group conversions to provide a set of substituted 4-HCPs in either enantiomeric form.

Tunable Visible Light Emission of Self-Assembled Rhomboidal Metallacycles

Supramolecular coordination complexes (SCCs) have been proposed for applications necessitating photon emitting properties; however, two critical characteristics, facile tunability and high emission quantum yields, have yet to be demonstrated on SCC platforms. Herein, a series of functionalized D2h [D2A2] rhomboids (D = 2,6-bis(4-ethynylpyridine)aniline-based ligands; A = 2,9-bis[trans-Pt(PEt3)2NO3]phenanthrene) is described with emission wavelengths spanning the visible region (λmax = 476-581 nm). Tuning was achieved by simple functional group modifications para to the aniline amine on the donor building block. Steady-state absorption and emission profiles were obtained for each system and are discussed. When the Hammett σ(para) constants for the functional groups para to the aniline amine were plotted versus the wavenumber (cm(-1)) for the λmax of the emission profile, a linear relationship was observed. By utilizing this relationship, the emission wavelength of a given rhomboid can be predetermined on the basis of the Hammett constant of the functionality employed on the donor precursor. This range of visible light emission for a suite of simple rhomboids along with the predictive nature of the wavelength of emission is unprecedented for these types of systems.

Evaluation of vitamin D3 A-ring analogues as Hedgehog pathway inhibitors

A structure-activity relationship study focusing on the A-ring of vitamin D3 (VD3) was undertaken to elucidate its role in inhibiting the Hedgehog pathway and in mediating anti-cancer effects. Analogues resulting from simple functional group substitution at 3' position of VD3 were evaluated in a variety of biological assays to determine their ability to selectively inhibit Hh signaling. Moderately active Hh inhibitors that have insignificant binding affinity for VDR were identified; however, these compounds also activate the traditional VDR pathway, presumably due to metabolites produced in the cultured cells. Thus, further structural modifications to the VD3 scaffold are required to yield potent, selective Hh inhibitors.

Sodium Borohydride‐Nickel Chloride‐Methanol Catalytic System for Regioselective Reduction of Electron‐Rich Conjugated Dienes and Reductive Cleavage of Allyl Esters Involving π‐Allylnickel Intermediates

AbstractThe regioslective reduction of electron‐rich dienes to monoolefins and the reductive cleavage of allyl esters were fulfilled by employing a sodium borohydride‐nickel chloride‐methanol catalytic system with exceedingly simple manipulations and high functional group tolerability. Both of the reductive reactions may involve π‐allylnickel intermediates generated from fresh nickel boride.