Protonation of γ-Butyrolactone and γ-Butyrolactam

Abstract : γ-Butyrolactone and γ-butyrolactam were reacted in the superacidic systems XF/MF₅ (X=H, D; M=As, Sb). Salts of the monoprotonated species of γ-butyrolactone were obtained in terms of [(CH₂)₃OCOH]⁺[AsF₆]⁻, [(CH₂)₃OCOH]⁺[SbF₆]⁻ and [(CH₂)₃OCOD]⁺[AsF₆]⁻ and the analogous lactam salts in terms of [(CH₂)₃NHCOH]⁺[AsF₆]⁻, [(CH₂)₃NHCOH]⁺[SbF₆]⁻ and [(CH₂)₃NDCOD]⁺[AsF₆]⁻. The salts were characterized by low temperature Raman and infrared spectroscopy and for both protonated hexafluoridoarsenates, [(CH₂)₃OCOH]⁺[AsF₆]⁻ and [(CH₂)₃NHCOH]⁺[AsF₆]⁻, single-crystal X-ray structure analyses were conducted. In addition to the experimental results, quantum chemical calculations were performed on the B3LYP/aug-cc-pVTZ level of theory. As in both crystal structures C⋅⋅⋅F contacts were observed, the nature of these contacts is discussed with Mapped Electrostatic Potential as a rate of strength.     

One-Pot Regioselective γ-Trifluoromethylthiolation and γ-Methylthiolation of Enals

We describe herein the direct electrophilic γ-trifluoromethylthiolation and γ-methylthiolation of enals, via the in situ formation of the corresponding silyl dienol ether. This one-pot process is carried out under simple and mild reaction conditions and is compatible with a variety of functional groups.     

Syntheses and structures of tetraphenylantimony γ-phenyl-and γ-thiobutylacetylacetonates

Tetraphenylantimony γ-phenylacetylacetonate (I) and tetraphenylstibium γ-thiobutylacetylacetonate (II) are synthesized by the reaction of pentaphenylantimony with γ-phenylacetylacetone or γ-thiobutylacetylacetone in toluene. According to the X-ray diffraction data, the antimony atoms in complexes I and II have a distorted octahedral coordination. In complex I, the Sb-C bond lengths are 2.155(2)–2.170(1) Å, and the Sb-O(1), Sb-O(2) and O(1)-C(2), O(2)-C(4) in the heterocycle are 2.215(1), 2.227(1) and 1.282(2), 1.277(2) Å, respectively. In complex II, the bond lengths are the following: Sb-C 2.147(3)–2.161(3), Sb-O(1, 2) 2.281(2), 2.215(2), and O-C 1.267(3)–1.278(3) Å.     

Synthesis of γ-mercuridinitrohydrocarbons

Summary The denitration of -mercurinitro compounds has been studied and the corresponding organomercury dinitro derivatives have been obtained.     

Synthese des γ-Fagarins

Es wird die analog der des Dictamnins durchgeführte Synthese des -Fagarins beschrieben.     

SYNTHESIS OF γ-GLUTAMYLPHOSPHONODIDEPEPTIDES

Abstract

γ-Glutamylphosphonodidepsipeptides 3a-f were obtained by condensation of α-t-butyl or α-benzyl ester of optically active N-benzyloxycarbonyl-glutamic acid with di-p-nitrobenzyl 1-hydroxymethanephosphonate, (+) dibenzyl 1-hydroxy-2-methylpropanephosphonate and (-) dibenzyl 1-hydroxy-3 methylbutanephosphonate. Dicyclohexylcarbodiimide in the presence of 4-(N,N-dimethylamino)- pyridine and 1-hydroxybenzotriazole in methylene chloride was used as a condensing agent for compounds 3a-c. Compounds 3d-f were obtained by means of the dicyclohexylcarbodiimide method in the presence of 4-(N, N-dimethylamino)pyridine in carbon tetrachloride. Protecting groups were removed by conventional methods.     

Purification of γ-Benzyl and γ-Methyl L-Glutamate N-Carboxyanhydrides by Rephosgenation

Rephosgenation of N-carboxyanhydrides of γ-benzyl and y-methyl L-glutamates, vs multiple recrystallizations, is a very efficient method for obtaining highly purified N-carboxyanhydrides, from which very high MW (0.98-1.5 × 10⁶ Daltons) polymers can be derived.     

Nitroalkylation and nitroalkenylation reactions of γ-lactone enolates. A facile ring switch from polysubstituted γ-lactones to polysubstituted γ-lactams

Michael addition of lithium enolates of γ-butyrolactone 1 and α-methyl-γ-butyrolactone 1′ to (E)-1-nitropropene 2, (E)-β-nitrostyrene 3 and (E)-2-nitro-1-phenylpropene 4 is described. Reactions of the lithium enolate of 1′ with 2 and 4 occurred with high diasteroselectivity (80 and 92% d.e., respectively). Reactions of the zinc enolate of 1′ with two β-nitroenamines and two methylthio-substituted 1-amino-2-nitro-1,3-dienes were also examined. Catalytic reduction of the nitroalkylated and nitroalkenylated products allowed the achievement of functionalized γ-lactams and/or cyclic hydroxamic acids.     

Enzymatic Synthesis of γ-Glutamylmethylamide from Glutamic Acid γ-Methyl Ester and Methylamine Catalyzed by Escherichia coli Having γ-Glutamyltranspeptidase Activity

A new method for the synthesis of γ-glutamylmethylamide is presented. Glutamic acid γ-methyl ester was used as substrate for γ-glutamylmethylamide synthesis catalyzed by Escherichia coli with γ-glutamyltranspeptidase activity. Reaction conditions were optimized by using 300 mM glutamic acid γ-methyl ester and 3,000 mM methylamine at pH 10 and 40 °C. Bioconversion rate of γ-glutamylmethylamide reached 87 % after 10 h. γ-Glutamyltranspeptidase was reversibly inhibited only when glutamic acid γ-methyl ester was above 300 mM.     

Ligand-Enabled Double γ-C(sp3)−H Functionalization of Aliphatic Acids: One-Step Synthesis of γ-Arylated γ-Lactones

γ-methylene C(sp³)−H functionalization of linear free carboxylic acids remains a significant challenge. Here in we report a Pd(II)-catalyzed tandem γ-arylation and γ-lactonization of aliphatic acids enabled by a L,X-type CarboxPyridone ligand. A wide range of γ-arylated γ-lactones are synthesized in a single step from aliphatic acids in moderate to good yield. Arylated lactones can readily be converted into disubstituted tetrahydrofurans, a prominent scaffold amongst bioactive molecules.     

The Battle of Calicheamicin γ

The first total synthesis of calicheamicin γ was achieved approximately a year ago. In this article, the author presents a personal account of the events, in chronological order, that led to this success story in total synthesis.     

A tandem Baylis-Hillman-singlet oxygen oxidation reaction for facile synthesis of γ-substituted γ-hydroxybutenolides

A series of highly functionalised γ-hydroxyacryl γ-hydroxybutenolides, 2, were synthesised in 25-50% overall yields in two or three steps from 2-furfural using a tandem Baylis-Hillman-singlet oxygen oxidation reaction.     

Synthesis and Antitumor Activity Evaluation of γ-Monofluorinated and γ,γ-Difluorinated Goniothalamin Analogues

A series of novel γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and 6a – 6i were synthesized. The key steps included the construction of C‐5 stereocenter adjacent to gem‐difluoromethylene group by way of lipase AK catalyzed kinetic resolution, the introduction of aryl group via Stille coupling, and lactonization by 1,5‐oxidative cyclization. These γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and their enantiomers 6a – 6i , together with several corresponding γ‐monofluorinated Goniothalamin analogues were biologically evaluated against four different cancer cell lines. Compound 7h showed a nearly equivalent potency as the parent (R)‐Goniothalamin in the micromolar range. The different fluorine effects between fluoromethylene and gem‐difluoromethylene on antitumor activity were discussed through the analysis of bioassay data.     

Synthesis of γ-butyrolactone fused cyclooctene

The expeditious route for the synthesis of γ-butyrolactone fused cyclooctene starting from the γ-butyrolactone fused cyclopentane through bicyclo[4.2.1]nonan-9-one is reported. Retro-Dieckmann’s condensation of bicyclo[4.2.1]nonan-9-one in presence of sodium methoxide and methanol furnished γ-butyrolactone fused cyclooctene in good yield. Surprisingly, the stereochemistry of ring-junction of γ-butyrolactone fused cyclooctene is different from the γ-butyrolactone fused cyclopentane, and the position of new ester group, which were confirmed unambiguously by X-ray analysis.     

Thermal Stability of γ-irradiated Tolbutamide

The thermal stability of tolbutamide before and after exposure to various γ-radiation doses was investigated. The data were followed by studying DTA, X-ray diffraction, IR, and UV absorption spectra before and after γ-irradiation. The results obtained were promising, and were explained, and discussed on the basis of γ-enhanced stabilization through recombination of free radicals. This revised version was published online in August 2006 with corrections to the Cover Date.     

Enantioselective synthesis of functionalized γ-butyrolactones

Sharpless asymmetric dihydroxylation and aminohydroxylation of (E)-dimethyl-2-alkylidene glutarates 2 were shown to afford enantio-enriched or enantiopure highly functionalized γ-butyrolactones 3 and 7.     

Synthesis of Some Novel γ-Spirolactones

Summary. We report on the addition of dialkyl acetylenedicarboxylate to 1-alkylisatins or tryptanthrine in the presence of triphenylphosphine which leads to highly functionalised novel unsaturated -spirolactones.