Poly(γ-alkyl glutamates). I

Good yields of some crystalline γ-alkyl esters of L -glutamic acid were obtained by carrying out the esterfication with a small (20–50 mole-%) excess of alcohol in aqueous hydrochloric acid or 60–80% sulfuric acid followed by neutralization with an alkaline solution. This new method made it possible to synthesize various γ-alkyl L -glutamates, including those higher than ethyl, and consequently, various poly(γ-alkyl L -glutamates) such as methyl, ethyl, n-propyl, n-butyl, isobutyl, and isoamyl. The conformation of these poly-L -glutamates in the solid state was determined by the infrared absorption method. The molecular motions of the polymers of γ-methyl, -ethyl, -n-propyl, -n-butyl, and-isoamyl L -glutamates and poly(γ-methyl-D -glutamate) in the solid state were studied by NMR, and dielectric and mechanical measurements. At temperatures up to 400°K., the NMR spectra of poly(γ-methyl D -glutamate) can be explained only by rotational motion of the side chain. Also, from NMR results, rotational motion of C?O groups in the side chain of poly(γ-methyl D -glutamate) is expected near room temperature, and such a motion was examined by dielectric measurements. Rotation of C?O groups in the side chains of polymers of γ-methyl, γ-ethyl, γ-n-propyl, γ-n-butyl, and γ-isoamyl L -glutamate was also observed near room temperature by dielectric measurements in the frequency range from 10² to 10⁶ cps. Activation energies obtained by dielectric and mechanical measurements were similar to those for the side chain motions of the corresponding esters of poly(methacrylic acid). Although it has been noted that the molecular motion of poly(γ-benzyl L -glutamate) in the solid state at room temperature may be related to the motion of its back bone, the molecular motion in these poly-L -glutamates at these temperatures can be explained only in terms of side-chain rotation.     

Syntheses of stereodefined β-alkylidene-γ-lactones and substituted β, γ-unsaturated δ-lactones

1-Trimethylsilyl-1,3-diyne derived trans-bis(trimethylstannyl) enynes undergo stepwise transmetallation with methyllithium to furnish the corresponding enynyllithium reagents. The application, in various orders, of a sequence of transmetallation-protonation-alkylation-hydroxyalkylation-hydroboration-oxidation reactions provides a novel approach to stereo-defined β-alkylidene γ-lactones and β, γ-unsaturated δ-lactones.     

Downfield γ-gauche and γ-antiperiplanar effects on 13C NMR chemical shifts exerted by thiophene sulphur

The γ-effects of sulphur on ¹³C NMR chemical shifts have been measured in a series of steroidal compounds containing the thiophene ring in different configurations with respect to the rest of the molecule. The data constitute the first example of downfield effects exerted by sulphur on both gauche and antiperiplanar γ-carbons. The γ-gauche effect of sulphur amounts to 1.6–1.8 ppm, the γ-antiperiplanar effect from practically zero to almost 1 ppm.     

The influence of short branches on the α, β and γ-relaxation processes of ultra-high strength polyethylene fibers

Dynamic mechanical measurements were conducted for several kinds of ultra–high-strength polyethylene fibers with different methyl branch contents. As is the case with conventional polyethylene materials, UHSPE fibers also exhibit α, β, and γ-relaxation dispersions. Each relaxation process is the function of both the tensile moduli and the branch contents of UHSPE fibers. It was also found that the γ-process of UHSPE fibers is dominated mainly by the localized molecular motion in the crystalline part, such as a dislocation mode of crystallite defects, which is very sensitive to the branching content. From the time and temperature superposition of the frequency dispersion experiments, it was found that activation energies for both the α2-process and α3-process increase proportionally to the methyl branch content, while the α1-process is not so affected by the branch content. This result shows that the incorporated branch sites in the crystalline part effectively hinder the chain-to-chain slippage; meanwhile, they have not hindered the slippage at the grain boundary so far, which also enables us to explain the creep improvement of UHSPE fibers through branch incorporation with the same mechanism. © 1994 John Wiley & Sons, Inc.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Mechanical relaxations in γ-ray-polymerized polyethylene

Dynamic mechanical properties of cold-compacted films of polyethylene prepared by γ-ray-induced polymerization in bulk at 30°C are discussed in connection with the fine structure. The cold-compacted films show a broad α-relaxation at a lower temperature than do single-crystal mats or melt-crystallized polymer. From the effects of annealing and swelling by carbon tetrachloride on the relaxation, it is concluded that the α-relaxation, like the α-relaxation in the single-crystal mats, originates from molecular motions within lamellar crystals. This is consistent with the finding that these films are composed of stacked small irregular lamellar crystals. The γ-relaxation is also similar to that in crystal mats.     

Kinetics of γ-ray polymerization of formaldehyde in the presence of carbon dioxide

A kinetic study of the γ-ray polymerization of formaldehyde in toluene solution in the presence of carbon dioxide was carried out at temperatures of + 13 to ?17°C. Two modes of the polymerization, spontaneous and γ-ray polymerization, occur in this system. The γ-ray polymerization, experimentally separated from the spontaneous polymerization, was investigated. The rate of γ-ray polymerization increased slightly with the square root of carbon dioxide concentration. The rate of polymerization was also found to be proportional to the dose rate and the square of monomer concentration. The molecular weight of polymer formed was independent of the reaction condition. The apparent activation energy was estimated to be 10.3 kcal./mole. The kinetics of the γ-ray polymerization in the presence of carbon dioxide are explained quantitatively by a cationic mechanism, and the role of carbon dioxide is as an action of retardation for neutralization of the cationic initiating species, which was produced by γ-radiation, by means of a reverse reaction with an electron. Physical and mechanical properties of the polymer obtained by γ-ray polymerization were also investigated.     

γ–α transformation in isotactic polypropylene

A γ-phase to α-phase transformation in a specimen of isotactic polypropylene crystallized under conditions of high pressure was induced by drawing at 100°C. X-ray studies showed that the unoriented component remained in the γ-phase, and that the oriented component was found only in the α-phase. This evidence supports a previous suggestion that the phase transformation is martensitic in character. The consequences of such an assumption are discussed. The role of dislocations in polymeric systems is generally believed to be not too significant, but since martensitic reactions involve cooperative movements of atoms, an exception in this case is suggested. A possible mechanism for the phase transformation is suggested.     

The Preparation of β-Cycloalkyl-L-Aspartate and γ-Cycloalkyl-L-Glutamate by Enzymatic Hydrolyses

The simple method to prepare the β-cycloalkyl aspartate and γ-cycloalkyl glutamate by enzymatic reactions has been developed. Compared with conventional chemical methods, the enzymatic method is more facile.     

α–γ transition in nylon 6

The α to γ transition that occurs in nylon 6 upon iodine treatment was investigated by infrared spectroscopy, differential thermal analysis, and x-ray diffraction techniques. Thin films of nylon (0.2 mil) were treated in either iodine–potassium iodide aqueous solution or in iodine vapor. Very short treatment times, in the order of 30 sec, were found to effect the transition when a solution 0.5M with respect to iodine was used. The infrared spectra of the iodine nylon complexes formed from either the α- or γ-nylon 6 treated in vapor or dissolved iodine were all similar. This is an indication that molecular iodine is the active species in forming the complex. The temperature of the washing solution used to remove the iodine from the nylon determines whether an α-nylon 6 or γ-nylon 6 is obtained from the complex after washing. Nylon 6 plaque surfaces and thin films are similar in their behavior towards the iodine treatment. The γ-nylon 6 is a stable modification at all temperatures below its melting point. The conversion of the γ form back to the α modification can occur only if the hydrogen bonding is severely affected, e.g., by phenol treatment, iodine treatment, melting, etc. Infrared spectroscopy provided no evidence for an α–γ transition in nylon 6 on heating the sample continuously through its melting point. The shapes of the melting peaks in the above two modifications of nylon 6 were sufficiently different to provide a means of identifying the two crystalline forms.     

Rhodium‐Catalyzed Asymmetric Arylation of β,γ‐Unsaturated α‐Ketoamides for the Construction of Nonracemic γ,γ‐Diarylcarbonyl Compounds

A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide.     

13C nuclear magnetic resonance spectra. XV—the γ-anti substituent effect and its dependence on substitution at the α- and γ-carbon atom

It is shown that the γ_α effects of hetero substituents on the ¹³C chemical shift (γ_α SCS) are enlarged by +2 to +5 ppm by substituting the α-hydrogen atom by any group or atom (e.g. CH₃, OR, F, Cl, Br). The same is encountered when the axial γ-hydrogen is replaced by CH₃, OH or F. If, however, the substituting atom at the γ_α-carbon atom is a higher-row halogen (Cl or Br), diamagnetic γ_α SCS for this signal are observed which may even exceed those for unsubstituted γ_α-carbon atoms. The removal of a 1,3-diaxial hydrogen-hydrogen interaction and the existence of a still unspecified ‘heavy halogen effect’–both diamagnetic contributions to the γ_γ SCS of hetero substituents–are responsible for these findings. Methyl groups do not behave like hetero substituents with respect to the γ_α SCS.     

Die Kristallstrukturen von Me3SiI · β-Picolin und Me3SiI · γ-Picolin Vergleich der Lewis-Basen Pyridin, β-Picolin und γ-Picolin

The Crystal Structure of Me₃SiI · β-Picoline and Me₃SiI · γ-Picoline A Comparison between the Lewis-Bases Pyridine, β-Picoline, and γ-Picoline The reaction of Iodinetrimethylsilane with β- und γ-Picoline (Pic) leads to solid 1 : 1 compounds Me₃SiI · β-Picoline 1 , Me₃SiI · γ-Picoline 2. The reaction was performed at room temperature. Yellow single crystals were obtained by sublimation. Single crystal X-ray investigations confirm that both compounds are ionic [Me₃SiPic]⁺I^?. The comparison of β-Picoline with γ-Picoline and Pyridine (Py) demonstrates that the presence of a methyl group and also its position has no significant influence on the Si? N bond length in compound 1, 2 and on the adduct Me₃SiI · Py.     

Reaktionen mit γ-Chloracetessigesterderivaten

Reactions with derivatives of γ-chloroacetoacetic acid Ethyl γ-chloroacetoacetate reacts with ammonia to give ethyl β-amino-γ-chloro-crotonate; with aniline, however, β-anilino-crotonic acid γ-lactone is formed. The reaction of ethyl α-cyano-γ-chloro-acetoacetate with arylamines yields 1-aryl-2-amino-3-ethoxycarbonyl-pyrrolin-4-ones.     

Comparative study of dielectric,mechanical, and nuclear magnetic relaxations in linear polyethylene. II. Relaxation spectroscopy of the α, β, and γ loss bands with special emphasis on fine structure

Dielectric, mechanical, and NMR retardation (correlation) spectra for relaxations in linear polyethylene were calculated in normalized form and intercompared. For each of the two local-mode relaxations in the γ region, called γ₁ and γ₂, these spectra are found to be in excellent agreement. For the α region, the spectra for two mechanical processes, called α₁ and α₂, two NMR processes, called α′ and α, and one dielectric process α were calculated. Excellent agreement is found between the spectra for the dielectric α and NMR α′ processes and also spectra for the mechanical α₂ and NMR α processes, due to molecular motion in the interior of crystals. However, the spectrum for the mechanical α₁ process is different from that for the dielectric α and NMR α′ processes, though the activation energy for the first process is almost the same as for the other two. This behavior is interpreted on the assumption that the dielectric α and NMR α′ processes are caused by molecular motion in lamellar surface layers while the mechanical α₁ process is due to grain-boundary slip with viscous resistance of the surface layers in the boundaries. The shapes of the spectra, including the spectrum for the β process, are not affected by diluent.     

Improved preparation and characterization of unsaturated γ-lactones

Improved, high yield procedures for the preparation of unsaturated γ-lactones (I-IV) from saturated γ-lactones (V) are described. Compounds V are first converted to the sodium salts of the corresponding γ-hydroxy acids (VI) (100%) which are oxidized within fifteen minutes to the γ-keto acids (VII) (75–85%) by bromine at pH 6-7.5. Acid-catalyzed reaction of VII with acetic anhydride at room temperature for fifteen minutes yields γ-acetoxy-γ-lactones (VIII) (70–90%). Pyrolysis of VIII at 200–330° yields I-IV (70–95%), the composition of which depends on whether strongly acidic contaminants have been completely removed from VIII prior to pyrolysis. In selected cases studied, fractional distillation permits the isolation of pure unsaturated lactones. Nmr has been extensively used to determine purity at each step and the composition of mixtures of I-IV.     

Efficient Access to Enantiopure γ4‐Amino Acids with Proteinogenic Side‐Chains and Structural Investigation of γ4‐Asn and γ4‐Ser in Hybrid Peptide Helices

Hybrid peptides composed of α‐ and β‐amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ‐ and hybrid γ‐peptides composed of γ⁴‐amino acids are less studied than their β‐counterparts. However, recent investigations reveal that γ⁴‐amino acids have a higher propensity to fold into ordered helical structures. As amino acid side‐chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ⁴‐residues with functional proteinogenic side‐chains and their structural analysis in hybrid‐peptide sequences. Here, the efficient and enantiopure synthesis of various N‐ and C‐terminal free‐γ⁴‐residues, starting from the benzyl esters (COOBzl) of N‐Cbz‐protected (E)‐α,β‐unsaturated γ‐amino acids through multiple hydrogenolysis and double‐bond reduction in a single‐pot catalytic hydrogenation is reported. The crystal conformations of eight unprotected γ⁴‐amino acids (γ⁴‐Val, γ⁴‐Leu, γ⁴‐Ile, γ⁴‐Thr(OtBu), γ⁴‐Tyr, γ⁴‐Asp(OtBu), γ⁴‐Glu(OtBu), and γ‐Aib) reveals that these amino acids adopted a helix favoring gauche conformations along the central C^γ? C^β bond. To study the behavior of γ⁴‐residues with functional side chains in peptide sequences, two short hybrid γ‐peptides P1 (Ac‐Aib‐γ⁴‐Asn‐Aib‐γ⁴‐Leu‐Aib‐γ⁴‐Leu‐CONH₂) and P2 (Ac‐Aib‐γ⁴‐Ser‐Aib‐γ⁴‐Val‐Aib‐γ⁴‐Val‐CONH₂) were designed, synthesized on solid phase, and their 12‐helical conformation in single crystals were studied. Remarkably, the γ⁴‐Asn residue in P1 facilitates the tetrameric helical aggregations through interhelical H bonding between the side‐chain amide groups. Furthermore, the hydroxyl side‐chain of γ⁴‐Ser in P2 is involved in the interhelical H bonding with the backbone amide group. In addition, the analysis of 87 γ⁴‐residues in peptide single‐crystals reveal that the γ⁴‐residues in 12‐helices are more ordered as compared with the 10/12‐ and 12/14‐helices.     

Dependence of the γ carbon-13 shielding effect on electronegativity

Three γ effects on ¹³C shielding in 3,3-dimethylheteracyclohexanes as a function of the hetero-atom X have been examined. The γ-anti effect on the equatorial 3-methyl group is small in absolute magnitude but strongly dependent on the polar properties of X. The plot of the ¹³C shielding of this carbon vs the electronegativity of X is linear, with a slope of ?5.8 ppm/electronegativity unit. The γ-gauche effects on the axial 3-methyl group and on the 4-carbon are large in absolute magnitude but have quite different dependences on the polar properties of X. Whereas the shielding of the 4-carbon exhibits a linear dependence on electronegativity (slope ?3.5), the axial 3-methyl group shows little dependence (slope crudely ?0.7), even though the geometric relationship between X and either carbon is almost the same. Neither gauche carbon shielding appears to be related to the steric properties of X. The polar component of both the γ-anti effect and the γ-gauche effect is interpreted as arising from overlap of appropriately positioned parallel orbitals. For the anti case, the pathway is the familiar zigzag arrangement of bonds. For the gauche case, the pathway may be either through space (the orbitals would be only on X and C-α; for the 4-carbon, this interaction would be through the center of the ring) or through bonds (there are parallel axial orbitals on all four atoms). The absence of a significant polar effect for the axial 3-methyl group suggests that the gauche interaction requires a rigid pathway. The polar component of the general γ-gauche effect is superimposed upon a larger contribution that is essentially independent of the nature of X and may be associated with the removal of the hydrogen on the β-carbon and replacement with the γ-X group.     

A New Type of Photorearrangement of γ-Hydroxy-α, β, δ, ε-dienone

A new type of photorearrangement of the γ-hydroxy-α, β, δ, ε-dienone, vomifoliol acetate ( 2 ) to the diketone 4 is described, and its facile rearrangement is compared with that of desoxyvomifoliol acetate ( 3 ).     

Syntheses of the Enantiomers of γ-Cyclogeranic Acid, γ-Cyclocitral,and γ-Damascone: Enantioselective protonation of enolates

(R)-and (S)-γ-cyclogeranic acid ((R)-and (S)- 9 , resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)- 9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)- 6 , resp.), and (R)-and (S)-γ-damascone ((R)-and (S)- 5 , resp.). A more direct entry to (R)-and (S)- 9 consisted in the enantioselective protonation of a thiol ester enolate with (?)- or (γ)-N-isopropylephedrine((?)- or (γ)- 20 ) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)- 24 , resp.; 97% ee). The esters (R)- and (S)- 24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)- 5 , resp.). Alternatively, (S)- 5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (?)-N-isopropylephedrine ((?)- 20 ). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.