Showing papers on "Substituent published in 1997"

Models for Nonheme Iron Intermediates: Structural Basis for Tuning the Spin States of Fe(TPA) Complexes

Abstract: Our efforts to model the oxygen activation chemistry of nonheme iron enzymes have yielded transient intermediates with novel properties. These properties can be dramatically affected by the introduction of a 6-methyl substituent on the pendant pyridines of the tetradentate ligand TPA (TPA = tris(2-pyridylmethyl)amine). A series of Fe(TPA) complexes has thus been synthesized and characterized to provide the structural basis for these dramatic effects. The following complexes have been obtained: [Fe(L)(CH3CN)2](ClO4)2 (1, L = TPA; 2, L = 6-MeTPA; 3, L = 6-Me2TPA; 4, L = 6-Me3TPA) and [Fe(L)(acac)](ClO4)2 (5, L = TPA; 6, L = 5-Me3TPA; 7, L = 6-MeTPA). As indicated by 1H NMR and/or EPR, 1, 5, and 6 with no 6-methyl substituent are low spin, while complexes 2, 3, 4, and 7 with at least one 6-methyl substituent are all high spin, with higher redox potentials than their low-spin counterparts. The ligands with 6-methyl substituents thus favor a metal center with a larger ionic radius, i.e., FeII over FeIII and h...

Model Studies for New o-Nitrobenzyl Photolabile Linkers: Substituent Effects on the Rates of Photochemical Cleavage.

Abstract: Both a model phenacyl and o-nitrobenzyl photolabile linker from the literature along with four new o-nitrobenzyl linkers were prepared and the kinetics of their photolytic cleavage examined in solution. The linkers were prepared by amidation of the carboxylic acid anchoring tether with benzylamine, and the cleavable benzylic substituent was chosen to be either acetic acid or acetamide. Irradiation of the linkers in four solvents (methanol, p-dioxane, and aqueous buffer ± dithiothreitol) at 365 nm and analysis via HPLC afforded kinetic rates of cleavage suitable for comparative purposes. The phenacyl linker was found to cleave slowly under aqueous conditions with no detectable cleavage being observed in the organic solvents. Known o-nitrobenzyl linker 4 showed modest rates of cleavage in aqueous and organic solvents. Incorporation of two alkoxy groups in the benzene ring to generate the veratryl-based linker 13a increased the rate of cleavage dramatically, and introduction of an additional benzylic methyl ...

Self-Assembly and Disassembly of Regioregular, Water Soluble Polythiophenes: Chemoselective Ionchromatic Sensing in Water

Abstract: The development of polythiophene (PT) derivatives with essentially 100% head-to-tail (HT) couplings1,2 has led to the discovery of materials that self-assemble both in solution and in the solid state. Light-scattering studies on regioregular, HTpoly(3-dodecylthiophene) (HT-PDDT) show that a supramolecular organization occurs via intermolecular aggregation.3 This solution aggregation is precursive to a microcrystalline, self-assembled structure which has been characterized by X-ray studies.1,2,4 Polythiophenes possessing this metastable organization evidence high electrical conductivities1,2,5-8 and very small bandgaps. Previous work in our lab has shown that both conformational order and solid state organization in regioregular PT derivatives are remarkably sensitive to the placement and nature of the substituent chains.1,6,7,9 This sensitivity provides the opportunity to design new conducting polymers in which self-assembly is controlled by environmental factors. One remarkable example is HT-2,5-poly(thiophene-3-propionic acid) (3, PTPA). This polymer was designed such that upon deprotonation, water soluble polythiophene salts are formed.10 Both 3 and its partially deprotonated derivative 5 undergo protein-like hydrophobic assembly, with subsequent H-bond stabilization, to generate a self-assembled conducting polymer aggregate. Varying the size of the counterion in the carboxylate polymer changes the effective steric bulk of the substituent. Small cations favor a self-assembled (purple) state and large cations can completely disrupt the aggregated phase. In fact, a remarkable chemoselective counterion size-dependent chromaticity (Figure 1) is observed for polymer 5. The UV-vis λmax can be varied over a 130 nm range (from purple to yellow) simply by changing the countercation. Initially, we prepared the carboxylate precursor polymer 2 using the Ni(dppp)Cl2 cross-coupling method for the synthesis of HT polythiophenes.5,6,9 This method leads to low molecular weights (Mn ) 1.5-3.0 K), low yields (<5%), and polymers that show variable ionic chromaticity. However, the regioregular oxazoline polythiophene (2) (Mn ) 8 K, PDI ) 1.2) is prepared (Scheme 1) from monomer11 1 in high yields (84%)

Steric Effects in the Ground and Excited States of Cu(NN)2+ Systems

Abstract: This investigation focuses on a series of pseudotetrahedral complexes of the form Cu(NN)2+, where NN denotes a 1,10-phenanthroline ligand with alkyl substituents in the 2 and 9 positions and the counterion is PF6-. In these copper(I) systems, steric effects are of considerable interest because the electronic configuration predisposes the reactive charge-transfer excited state to undergo a flattening distortion or to add a fifth ligand. Both effects lead to emission quenching and a shorter excited-state lifetime. Bulky substituents inhibit these processes, but the spatial distribution of the atoms involved is more important than the total molecular volume in determining the influence of a substituent. According to the results of this study, the effective size decreases in the following order: sec-butyl > neopentyl > n-octyl ≈ n-butyl > methyl. In conjunction with the electrochemical data, the absorption and the emission spectra reveal three kinds of steric effects: (1) Clashes between substituents on opp...

Theoretical Calculation of Substituent Effects on the O−H Bond Strength of Phenolic Antioxidants Related to Vitamin E

Abstract: Calculations on phenol and a large number of phenols substituted with methyl, methoxyl, and amino groups have yielded reliable gas-phase O−H bond dissociation energies, BDE(ArO−H)gas. Geometries for the phenol, ArOH, and aryloxyl radical, ArO, were optimized at the (semiempirical) AM1 level followed by single point density functional theory (DFT) calculations using a 6-31G basis set supplemented with p-functions on the hydrogen atom and the B3LYP density functional. This gave BDE(PhO−H)gas = 86.46 kcal/mol, which is in good agreement with the experimental value of 87.3 ± 1.5 kcal/mol. All but one of the compounds and conformations examined had weaker O−H BDE's than phenol, the exception being o-methoxyphenol with the O−H group pointing toward this substituent (BDE = 87.8 kcal/mol). Where comparison was possible, calculated differences in O−H BDE's were in excellent agreement with experiment (better than 1 kcal/mol). A simple group additivity scheme also gave excellent agreement with calculated BDE (ArO−H)...

Rapid Solution and Solid Phase Syntheses of Oligo(1,4-phenylene ethynylene)s with Thioester Termini: Molecular Scale Wires with Alligator Clips. Derivation of Iterative Reaction Efficiencies on a Polymer Support

Abstract: The syntheses of soluble oligo(2-alkyl-1,4-phenylene ethynylene)s via an iterative divergent/convergent approach starting from 1-(diethyltriazyl)-3-alkyl-4-[(trimethylsilyl)ethynyl]benzenes are described. When the solublizing alkyl group is an ethyl substituent, the monomer, dimer, tetramer, and octamer can be synthesized. The octamer, however, is only minimally soluble. When the alkyl substituent is 3-ethylheptyl or dodecyl, the compounds are easily dissolved even at the 16-mer stage. The 16-mer is 128 A long in its near-linear extended conformation. At each stage in the iteration, the length of the framework doubles. Only three sets of reaction conditions are needed for the entire iterative synthetic sequence: an iodination, a protodesilylation, and a Pd/Cu-catalyzed cross coupling. Synthesis of the dodecyl-containing 16-mer was also achieved on Merrifield's resin using the iterative divergent/convergent approach. The oligomers were characterized spectroscopically and by mass spectrometry. The optical ...

4-aminoquinazoline derivatives

Abstract: Disclosed are novel 4-aminoquinazoline derivatives of the formula (See formula I) (wherein Z is NR3R4 in which R3 is H and R4 is Q2 or phenyl substituted with (R5)q or Z is (See formula II) the dotted line represents an optional double bond; R5 is a substituent such as halo, amino, alkyl, alkoxy, etc.; R6 is a substituent such as hydroxyl, amino, sulfo, alkoxy, carboxyl, etc.; q is 0-3; o is 0-2; Q2 is a 9- or 10-membered bicyclic heterocyclic moiety; Q1 is Ar-Y-X in which Ar is mono- or bicyclic (hetero)aryl, X is alkenylene, alkynylene or bond and Y is (CH2)p where p is 0-5; R1 is a substituent such as trifluoromethyl; n is 0-3; m is 1-2) and their pharmaceutically acceptable salts. Those compounds and the salts are useful for the treatment of hyperproliferative disorders and conditions in mammals.

A stable thiazol-2-ylidene and its dimer

Abstract: The synthesis, characterization and X-ray crystallographic structure determination are described for a stable thiazol-2-ylidene 2. This thiazol-2-ylidene is the first example of a stable, crystalline carbene in which the singlet carbene center bears a sulfur substituent. The carbene 2 is the closest stable analog of the important thiamin (vitamin B1) carbene. Although the thiazol-2-ylidene 2 is sufficiently stable to isolate at room temperature in the absence of moisture and oxygen, it will dimerize to form a normal carbene–carbene dimer {2}2. With the isolation and structure determination of both 2 and {22}, this system is the first in which a stable carbene and its corresponding dimer have been isolated and characterized. Additionally reported is the “reduced” 2H-thiazoline 2 · H2 in which the former carbene center in 2 has been reduced to a methylene (CH2) group. Thiazol-2-ylidenes with smaller groups on nitrogen (e.g. mesityl or methyl) are too unstable to allow easy isolation. The dimer from 3,4,5-trimethylthiazol-2-ylidene possesses a very unusual geometry in which one of the former carbene centers is planar while the second is pyramidal.

Carbene-Pnictinidene Adducts

Abstract: The syntheses, characterizations, and X-ray crystallographic structure determinations are described for adducts of stable nucleophilic carbenes with pnictinidenes. The adducts between 1,3-dimesitylimidazol-2-ylidene and phenylphosphinidene, phenylarsinidene, (trifluoromethyl)phosphinidene, and (pentafluorophenyl)arsinidene are reported. These carbene-pnictinidene adducts are formed by the direct reaction of a stable nucleophilic carbene with the corresponding pnictinidene cyclic oligomers. The synthesis and structure of the adduct between 1,3-dimesitylimidazolin-2-ylidene and phenylphosphinidene from the reaction of 1,3-dimesitylimidazolin-2-ylidene with phenylphosphorus dichloride are also reported. These carbene-pnictinidene adducts possess strongly polarized pnictinidene-carbene bonds. The C-Pn-C angles are all typically small at 97-102 degrees, and there is only a 4% shortening of the nominal Pn=C double bond compared to the Pn-C single bond to the second substituent on the pnictogen. The (31)P NMR shifts of the phosphorus adducts suggest strongly shielded phosphorus centers in accord with the polarized structures.

A Computational Analysis of Substituent Effects on the O-H Bond Dissociation Energy in Phenols: Polar Versus Radical Effects

Abstract: O−H bond dissociation energies (BDEs) of phenol, p-aminophenol, and p-nitrophenol have been computed using ab initio and density functional theory (DFT) methods. The MP2 and MP4 methods consistently overestimate the absolute BDEs but provide reasonable relative BDEs. Spin projected MP2 and MP4 energies are not able to reproduce the substituent effects on the BDE. The BLYP and B3LYP DFT methods provide more reliable and economical approaches for prediction of phenol BDEs. B3LYP/6-31G** computed ΔBDEs for 10 substituted phenols have been compared with values determined by different experimental approaches. The computed values are in most cases within the uncertainty of the measurements. It is shown that the substituent effects on the BDEs can be interpreted in terms of polar and radical stabilization. The polar stabilization is found to be related to the ability of the substituent to delocalize the lone pair on the phenol oxygen. The radical stabilization is dependent on the degree of spin delocalization. A...

Effect of counterions on properties of micelles formed by alkylpyridinium surfactants .1. Conductometry and H-1-NMR chemical shifts

Abstract: This paper delineates the influence of counterions on the aggregation behavior of 1-methyl-4-n-dodecylpyridinium surfactants, using conductometry and 1H-NMR spectroscopy. Three types of counterions have been studied: (i) halides, (ii) alkanesulfonates, and (iii) aromatic counterions. The critical micelle concentration is found to decrease with increasing counterion size and increasing counterion hydrophobicity, whereas the degree of counterion binding increases. The aggregation behavior of 1-methyl-4-n-dodecylpyridinium surfactants with aromatic counterions is shown to be markedly dependent on the substituent (hydrophobicity) and the substitution pattern in the aromatic ring of the counterion. Depending on the molecular architecture of the aromatic counterion, extremely long wormlike micelles can be formed instead of (nearly) spherical micelles. NMR experiments revealed that all aromatic counterions intercalate in between the pyridinium headgroups of the micelles, with more or less the same degree of pen...

Polymerization catalyst systems comprising substituted hafnocenes

Abstract: The present invention relates to a process for the polymerization of monomers utilizing a bulky ligand hafnium transition metal metallocene-type catalyst compound, to the catalyst compound itself and to the catalyst compound in combination with an activator. The hafnocene comprises at least one cyclopentadienyl ligand including at least one linear or isoalkyl substituent of at least 3 carbon atoms.

Active Site Models for Galactose Oxidase. Electronic Effect of the Thioether Group in the Novel Organic Cofactor.

Abstract: The electronic effect of the thioether linkage between Tyr 272 and Cys 228 (the novel organic cofactor) of galactose oxidase has been examined by using model compounds, 2-(methylthio)-p-cresol (1H), 2-(methylthio)-4,6-dimethylphenol (2H), and 2-(methylthio)-4-methyl-6-[[bis[2-(2-pyridyl)ethyl]amino]methyl]phenol (3H), the physicochemical properties of which are compared to those of 2-[[bis[2-(2-pyridyl)ethyl]amino]methyl]-4-methylphenol (4H) and p-cresol (5H). 1H NMR and electrochemical studies indicate that the methylthio group has essentially an electron-donating nature. On the other hand, the lower pKa values of 1H and 2H as compared to that of 5H suggest that the methylthio group also has a 2pπ−3dπ electron conjugative effect, stabilizing the negative charge on the phenolate oxygen. Furthermore, the electron-sharing conjugative effect of the substituent in the radical state has been clearly demonstrated by ESR studies and semiempirical molecular orbital calculations. Dimer copper(II) complexes [CuII2(...

Experimental and Theoretical Evidence of Through-Space Electrostatic Stabilization of the Incipient Oxocarbenium Ion by an Axially Oriented Electronegative Substituent During Glycopyranoside Acetolysis

Abstract: The rate of acetolysis of methyl 2,3,6-tri-O-methyl-α-d-galacto- and -glucopyranosides depends strongly on the electronegativity of the C4 substituent. Thus, of the three derivatives studied (4-methoxy, 4-acetoxy, and 4-acetamido-4-deoxy derivatives of d-galacto- and d-glucopyranosides), the glycopyranosides bearing the most electronegative C4 substituent (methoxy group) acetolyze at the fastest rate, whereas those having the least electronegative C4 substituent (N-acetamido group) acetolyze at the slowest rate. Furthermore, whereas the influence of the electronegativity of the C4 substituent upon the acetolysis rate in the d-gluco series is relatively moderate (kmax/kmin = 2.9−3.5), this influence is very large in the d-galacto series (kmax/kmin = 44.4−58.6). We propose that this observation can only be explained by the existence of an electron donation process from the axially oriented electronegative substituent at the C4 carbon atom of the galactopyranoside ring to the forming oxocarbenium ion. Such a...

Toward an understanding of the high enantioselectivity in the osmium-catalyzed asymmetric dihydroxylation. 4. Electronic effects in amine-accelerated osmylations

Abstract: Electronic effects in osmylation reactions accelerated by pyridine and quinuclidine derivatives were investigated by varying the substituents on the amine ligand as well as on the alkene substrate. Ligand substituent effects were gauged by determination of the equilibrium constants for coordination of the amines to OsO4, evaluation of structural properties and reduction potentials of the amine−OsO4 complexes, and analysis of the kinetics of osmylations in the presence of the amines. Substrate substituent effects were gauged by kinetic Hammett studies using several different amine/alkene combinations. Nonlinear Hammett relationships resulting from alkene substituent effects were observed, and the deviation from a linear free energy relationship was found to depend on the structure, binding capacity, and concentration of the amine. The results were evaluated in terms of the contending “[3 + 2]” and “[2 + 2]” mechanisms currently under consideration. A change in mechanism that depends on the structural and e...

Photogeneration of Fluoride by the Fluoroquinolone Antimicrobial Agents Lomefloxacin and Fleroxacin

Abstract: The photolysis (> 320 nm) of the fluoroquinolone antibacterial agents lomefloxacin and fleroxacin results in the loss of their F3 atoms as fluoride. The quantum yield for lomefloxacin was 0.98 at pH 7.4. The mechanism probably involves aryl-F heterolysis from the S1 state with the concomitant generation of a carbene at C-8. In contrast, the monofluorinated fluoroquinolones norfloxacin and ciprofloxacin do not generate fluoride upon irradiation. Carbenes are highly reactive species that undergo addition, insertion and abstraction reactions and can cause DNA cleavage. These findings may explain why lomefloxacin and fleroxacin are more photomutagenic and photocarcinogenic than fluoroquinolones in which C-8 is either unsubstituted or bears a substituent other than fluorine.

Ultraviolet absorption polymer comprising specific substituent and based on 2'-hydroxyphenyl benztriazole and photographic element containing it

Abstract: PROBLEM TO BE SOLVED: To provide a photographic element having large specific resistance against light, good stability of dyes in an image and showing low density of optical induced yellow discoloration, by incorporating a specified polymer UV- absorbent. SOLUTION: This photographic element contains a photosensitive part and an UV-absorbing polymer. The UV-absorbing polymer contains repeating units of 2'-hydroxyphenyl benzotriazole having substituents in 5- or 6-position selected from halogen, cyano, carboxyl or sulfonyl groups, and 4'-alkoxy groups bonded to the polymer chain. The alkylene part of the alkoxy group consists of, successively, a first bivalent connecting group, then an oxygen, sulfur or amino group, and a second bivalent connecting group bonded to the polymer chain (however, it has no substituent in the 3'-position and does not have any of -NH-, -OH and -SH in the 4'-position).

A General Synthetic Entry to Strychnos Alkaloids of the Curan Type via a Common 3a-(2-Nitrophenyl)hexahydroindol-4-one Intermediate. Total Syntheses of (±)- and (−)-Tubifolidine, (±)-Akuammicine, (±)-19,20-Dihydroakuammicine, (±)-Norfluorocurarine, (±)-Echitamidine, and (±)-20-Epilochneridine1

Abstract: A general strategy for the synthesis of pentacyclic Strychnos alkaloids with the curan skeleton has been developed. It utilizes 3a-(2-nitrophenyl)hexahydroindol-4-one (23), which was prepared from 2-allyl-2-(2-nitrophenyl)-1,3-cyclohexanedione (15), as the common, pivotal intermediate. Three different procedures have been employed for the closure of the bridged piperidine D ring from 23: (i) an intramolecular Michael-type conjugate addition; (ii) a Ni(COD)2-promoted biscyclization that assembles B and D rings in a single synthetic step, and (iii) an intramolecular cyclization of an enone−propargylic silane system. When necessary, depending on the procedure used, introduction of the oxidized one-carbon substituent at C-16, closure of the indole ring, and/or adjustment of the functionality of the C-20 two-carbon chain constitute the last stages of the synthetic route to the title alkaloids. The procedure involving the cyclization of a propargylic silane has been successfully extended to the enantiospecific...

Synthesis, 9Be NMR Spectroscopy, and Structural Characterization of Sterically Encumbered Beryllium Compounds

Abstract: The use of the terphenyl substituent −C6H3-2,6-Mes2 (abbreviated Ar) has permitted the synthesis of several new low-coordinate beryllium compounds. Reaction of 1 equiv of LiAr with BeCl2(OEt2)2 or ...

Substituent effects on the 15N NMR Parameters of Azoles

Abstract: The 15N chemical shifts and a large collection of coupling constants pertaining to azoles have been gathered from the literature. To complete this collection and to check some anomalies, the spectra of 14 compounds in several solvents were recorded again and 31 compounds were studied for the first time; in all, data for 420 compounds (pyrroles, imidazoles, pyrazoles, triazoles, tetrazoles, indoles, benzimidazoles, indazoles, benzotriazoles and carbazoles) are reported. Additive models are used to discuss the substituent chemical shifts. © 1997 by John Wiley & Sons, Ltd.

Synthesis and Reactions of 1,2-Cyclopropanated Sugars

Abstract: Diastereospecific cyclopropanation of glycals 1, 2, 3, 4, and 41 was carried out using either dihalocarbene addition or zinc-carbenoid addition to yield 1,2-cyclopropanated sugars. Dichloro- and dibromocarbenes added stereoselectively anti to the C3 benzyloxy group, whereas (under Simmons−Smith conditions) the cyclopropanes were formed syn to the same substituent. The reactions of these 1,2-cyclopropanated sugars to provide either ring expanded glycosides or C2-branched chain glycosides were explored. Solvolytic ring expansion of 1,2-dibromocyclopropanated sugars with K2CO3 in refluxing methanol yielded the corresponding chiral oxepins 20−22. Electrophilic ring openings of parent cyclopropanes (14 and 17 derived from glucal 1) were carried out with different electrophiles to give functionalized 2-deoxy-2-C-branched chain glycosides. The ring openings of 14 in different solvents resulted in both α- and β-anomers, whereas 17 gave exclusively the α-anomer.

Ab Initio Calculations on 2,6-Dimethylphenol and 4-(2,6-Dimethylphenoxy)-2,6-dimethylphenol. Evidence of an Important Role for the Phenoxonium Cation in the Copper-Catalyzed Oxidative Phenol Coupling Reaction

Abstract: Ab initio unrestricted Hartree−Fock calculations with a 6-31G* basis set were performed on 2,6-dimethylphenol (DMP or monomer) and 4-(2,6-dimethylphenoxy)-2,6-dimethylphenol (dimer) to gain more insight into the mechanism of the copper-catalyzed oxidative phenol coupling reaction. Atomic charges were determined for the phenol, phenoxyl radical, phenolate anion and phenoxonium cation (both the singlet and triplet state) of both species. Calculations for the monomer show that the only aromatic carbon atom bearing a partial positive atomic charge is the para carbon of the cation in the singlet state. In the case of the dimer, the presence of a p-phenoxy substituent results in a partial positive charge for the para carbon of the first aromatic ring in all states, but this charge is significantly higher for the singlet cation. In the singlet cationic state, the para carbon of the first aromatic ring is therefore the site most susceptible to nucleophilic aromatic substitution. This result strongly supports a pr...

Synthesis of ruthenium or osmium metathesis catalysts

Abstract: The present invention relates to the synthesis of highly active ruthenium and osmium carbene metathesis catalyst in good yield from readily available starting materials The catalysts that may be synthesized are of general formula (I) wherein: M is ruthenium or osmium; X and X1 are independently any anionic ligand; L and L1 are any neutral electron donor ligand; and, R and R1 are each hydrogen or one of the following substituent groups: C?2?-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkyl, aryl, C1-C20 carboxylate, C1-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20 alkylthio, C1-C20 alkylsulfonyl and C1-C20 alkylsufinyl Optionally, the substituent group may be substituted with one or more groups selected from C1-C5 alkyl, halogen, C1-C5 alkoxy, and aryl When the substitute aryl group is phenyl, it may be further substituted with one or more groups selected from a halogen, a C1-C5 alkyl, or a C1-C5 alkoxy Specific synthetic protocols for vinyl alkylidene catalysts wherein R is hydrogen and R?1? is -CHCR12R13 and non-vinyl alkyldiene catalysts are also disclosed In addition to the ease of synthesis (typically a one-step synthesis), the reactions generally may be run at or above room temperature and the resulting products usually may be used without extensive post synthesis purification

Formation of Dihydropyridone- and Pyridone-Based Peptide Analogs through Aza-Annulation of β-Enamino Ester and Amide Substrates with α-Amido Acrylate Derivatives

Abstract: The aza-annulation of β-enamino ester and amide substrates with the mixed anhydride of 2-acetamidoacrylic acid was used for the efficient construction of highly substituted α-acetamido δ-lactam products. With the α-acetamido substituent, lactam functionality, and γ-carboxylate group, these δ-lactam products represent an interesting class of conformationally restricted dipeptide analogs. The framework of this lactam hub is structurally related to that of an α-amino acid coupled with a β-amino acid. When α-amino esters derived from naturally occurring amino acids were used in the enamine formation step, subsequent aza-annulation led to branched peptide surrogates with two C-termini that extended from a common N-terminus. Oxidation of the aza-annulation products resulted in the generation of a planar system with peptide functionality radiating from the 1, 3, and 5 positions of the pyridone hub. Alternatively, pyridone products could be formed directly from the enamino amides by reaction with 2-phenyl-4-(etho...