Synthesis of γ-benzyltert-butoxycarbonyl-L-alanyl-D-glutamate and its derivatives

A convenient method of obtaining Boc-L-Ala-D-iGln-OBzl and its amide analogs by condensing the N-hydroxysuccinimidyl ester of Boc-L-Ala with the -benzyl ester ofD-Glu in the presence of NaHCO₃, followed by amidation of the resulting Boc-L-Ala-D-Glu--OBzl, is proposed. The use of l-adamantylamine and octadecylamine as amino components has enabled the corresponding -adamantylamide and octadecylamide of the dipeptide to be obtained.Simferopol' State University, 4 Yaltinskaya ul., Simferopol', Crimea, Ukraine 333036. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 101–103, January–February, 1998.     

Toward the synthesis of γ-pyrone-containing natural products: diastereoselective aldol-type reaction of a γ-pyrone

The diastereoselective aldol-type reaction of a γ-pyrone via a sodium anion has been developed. This reaction is useful for synthesizing γ-pyrone-containing natural products. Also, we applied the Mukaiyama aldol-type reaction of silyl enol ether of γ-pyrone by using TiCl₄. This Mukaiyama aldol-type reaction of γ-pyrone indicated higher anti-aldol selectivity than the aldol-type reaction of a γ-pyrone with NaHMDS.     

The photochemical and thermal reactions of a triosmium cluster carrying a γ-pyrone ligand with alkynes

The reaction of the cluster Os₃(CO)₁₀(μ-H)(μ-γ-C₅H₃O₂) (1) with a number of alkynes under thermal or visible light irradiation conditions, afforded in most cases the dinuclear complexes Os₂(CO)₆(μ-γ-C₅H₃O₂)(μ-LH) (L=PhCCPh, ^tBuCCH, ^tBuCCMe or EtCCEt) (2) or the trinuclear chain complexes Os₃(CO)₉(μ-H)(μ-γ-C₅H₃O₂)(μ-RCCHC₆H₄) (R=H, Ph) (3). In the case of PhCCPh, a new isomer of Os₃(CO)₈(PhCCPh)₂, viz., Os₃(CO)₈(μ-PhCCPh)(μ-PhCCHC₆H₄) (7) has been isolated and characterised.     

Cytotoxic principles and α-pyrone ring-opening derivatives of bufadienolides from Kalanchoe hybrida

Purification of the cytotoxic fractions of the methanol extracts of Kalanchoe hybrida leads to three new compounds with the basic skeleton of α-pyrone ring-opening products of bufadienolides, namely, kalanhybrin A-C (1-3). Moreover, four bufadienolides (4-7) and eight other compounds were also characterized from the title plant. The isolated compounds (1-7) were evaluated for their cytotoxicity toward MCF-7, NCI-H460, and SF-268 tumor cell lines. Among them, compounds 4 and 6 displayed significant cytotoxicity toward MCF-7 and NCI-H460 tumor cell lines at the tested concentration. In addition, the biosynthetic pathway of these α-pyrone ring-opening derivatives was also proposed.     

Preparation and antibacterial activity of aromatic derivatives of β-aminopropionic and γ-aminobutyric acid

Ten aromatic derivatives of β-aminopropionic acid and γ-aminobutyric acid were prepared.Their compositions and structures were identified by elemental analysis,IR,and 1H NMR.They have been examined for their antibacterial action against Staphylococcua aurens and Escherichia coli.These compounds showed higher activity than the aromatic derivatives of ct-amino acid which were reported previously.The general conclusion to be drawn is that the distance between amino and carboxylic group in these molecules could affect their antibacterial activity.Furthermore,those compounds with p-methyl substituent in phenyl ring exhibit higher activity than the others,and all the compounds exhibit higher activity against Escherichia coli and against Staphylococcua aureus.     

Efficient and green syntheses of novel γ-aminophosphonate and phosphine oxide derivatives

Two synthetic protocols leading to novel γ-aminophosphonate and phosphine oxide derivatives, by reductive amination of γ-phosphonylketones, are reported. The first method involved a two-step procedure. Imine intermediates were first isolated from the p-toluenesulfonic acid-catalyzed reaction of primary amines with γ-ketophosphonates and phosphine oxides, then reduced with NaBH₄ in refluxing ethanol. The second method consists of a one-pot procedure which includes the condensation of γ-ketophosphonates and phosphine oxides with primary amines, in the presence of molecular sieves, followed by reduction with NaBH₄. These methods offer significant advantages over prior reports, such as efficiency, generality, and good yields. Furthermore, they are green protocols avoiding hazardous hydrides and solvents.     

γ-Carbolines and their hydrogenated derivatives 3.* Hydrogenated derivatives of γ-carbolines: chemical and biological poperties (Review)

Published data on the chemical transformations and biological properties of dihydro-, tetrahydro-, and hexahydro-γ-carbolines are reviewed.     

Reaction of imidazole and its 2-alkyl derivatives with γ-butyrolactone

Reaction of imidazole with -butyrolactone gives N-alkylation and N-acylation products depending upon the reaction conditions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1491–1493, November, 1992.     

Experimental and theoretical thermochemistry of β-tetralone

The standard (p^° = 0.1 MPa) molar enthalpy of formation β-tetralone was measured, at T = 298.15 K, by static bomb calorimetry and the standard molar enthalpy of vaporization, at T = 298.15 K, was obtained using Calvet microcalorimetry.These values were used to derive the standard molar enthalpy of formation of the compound in the gaseous phase, at T = 298.15 K, ?(75.2 ± 2.5) kJ · mol^?1.Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy function with extended basis sets and more accurate correlated computational techniques of the MCCM/3 suite have been performed.     

Impact of the ΔPhe configuration on the Boc-Gly-ΔPhe-NHMe conformation: experiment and theory

Conformational propensities of N-t-butoxycarbonyl-glycine-(E/Z)-dehydrophenylalanine N′-methylamides (Boc-Gly-(E/Z)-ΔPhe-NHMe) in chloroform were investigated by NMR and IR techniques. The low-temperature crystal structure of the E isomer was determined by single crystal X-ray diffraction and the experimental data were elaborated by theoretical calculations using DFT (B3LYP, M06-2X) and MP2 approaches. The β-turn tendencies for both isomers were determined in the gas phase and in the presence of solvent. The obtained results reveal that the configuration of ΔPhe residue significantly affects the conformations of the studied dehydropeptides. The tendency to adopt β-turn conformations is significantly lower for the E isomer (Boc-Gly-(E)-ΔPhe-NHMe), both in gas phase and in chloroform solution.

     

Trienic α-pyrone and ochratoxin derivatives from a sponge-derived fungus Aspergillus ochraceopetaliformis

A new trienic α-pyrone derivative asteltoxin G (1) bearing a tetrahydrofuran ring and a new ochratoxin derivative named ochratoxin A₁ (5), along with seven known compounds, were isolated from a sponge-derived fungus Aspergillus ochraceopetaliformis. The compounds (1–9) were evaluated on the basis of spectroscopic analyses and comparison with those of the reported data. The new compound ochratoxin A₁ (5) exhibited anti-inflammatory activity against IL-6 and TNF-α expression of the LPS-induced THP-1 cells with inhibitory rates of 74.4 and 67.7% at concentration of 10 μM, respectively.     

Injection port silylation of γ-hydroxybutyrate and trans-hydroxycrotonic acid: conditions optimisation and characterisation of the di-tert-butyldimethylsilyl derivatives by GC-MS

Silylation is usually carried out on γ-hydroxybutyrate (GHB) for its analysis by Gas Chromatography/Mass Spectrometry (GCMS) and requires potentially long incubation times before injection during which the derivatisation reagent and derivatives (such as trimethyl-silyl compounds) can hydrolyse. Moreover, alternative internal standards (IS) are often useful depending on sample matrices, extraction/purification procedures, commercial availability and price. This study evaluated the possibility of silylating GHB with an injection port derivatisation procedure using N-methyl-N-[tert-butyldimethyl-silyl]trifluoroacetimide (MTBSTFA) with 1% tert-butyldimethylchlorosilane (TBCS) as the derivatisation reagent, producing di-tert-butyldimethyl-silyl derivatives as a novel means of analyzing GHB. In parallel, trans-hydroxycrotonic acid (t-HCA) was investigated as a potential IS for GHB quantification. Analyses were carried out with a temperature programmable injector and the GHB(t-BDMS)(2) and t-HCA(t-BDMS)(2) derivatives were successfully produced, characterised and derivatisation conditions optimised. t-HCA behaved very similarly to GHB through the derivatisation processes and was used as the IS for the determination of urinary endogenous GHB concentrations in human subjects where the method showed a limit of detection of 0.049 μg mL(-1), a limit of quantification of 0.162 μg mL(-1), and a limit of confirmation of 1.33 μg mL(-1), suitable for toxicological GHB concentration determination.     

Palladium-catalyzed epimerization of γ-alkenyl-γ-butyrolactone derivatives

γ-Alkenyl-α,β,γ-trisubstituted-γ-butyrolactones (12-16) and γ-alkenyl-furofurandione derivatives (21-Z-24-Z; 21-E-24-E; 25-Z-28-Z; and 25-E-28-E) were successfully epimerized in high yield by a palladium catalyst.     

Stability of pyrrolidone derivatives against γ-ray irradiation

To evaluate the stability of N-alkylated pyrrolidone derivatives(NRPs),which are supposed to be used as precipitants for U(VI) and Pu(IV,VI) species in HNO 3 media,under irradiation environment,some candidate NRPs were irradiated by γ-ray.Irradiation to HNO 3 solutions up to 6 mol dm 3(= M) containing 2 M N-n-butyl-2-pyrrolidone(NBP),one of NRPs with lower hydrophobicity,has revealed that the residual ratios of NBP in the samples of HNO 3 up to 3 M decreased identically and linearly.Approximately 20% of NBP was found to be degraded after the irradiation at 1 MGy.It was also found that the decrease in the precipitation ratio of UO 2 2+(P.R.,%) was gentle and that the P.R.values were relatively in accordance with the residual ratios of NBP.On the other hand,the degradation of the samples irradiated in 6 M HNO 3 was found more distinguished.It was proposed from the analyses of degraded compounds that the degradation of NBP in HNO 3 by γ-ray irradiation started from the cleavage of the pyrrolidone ring by the addition of oxygen atom originating from HNO 3,followed by the formation of chain compounds by the successive addition of oxygen,leading to the generation of oxalic acid and acetic acid.The stability of other NRPs in 3 M HNO 3 was evaluated to be nearly identical with that of NBP except lower P.R.values of the samples containing NRPs with higher hydrophobicity irradiated at more than 0.5 MGy.     

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.     

Effect of β- and γ-cyclodextrins and their methylated derivatives on the degradation rate of benzylpenicillin

Benzylpenicillin is characterized by instability in aqueous media, low oral bioavailability, and short biological half-life. Since their degradation products can cause allergic reactions, β-lactam antibiotics are supplied as a powder for injection and require special precaution when stored and re-constituted in water. An efficient method for β-lactam stabilization in the aqueous environment could reduce allergic side effects and facilitate their handling. Previously we proposed that complexation with cyclodextrins (CDs) is a way to achieve this goal. The purpose of the present study was to investigate the effect of methylation of CD on the chemical stability of benzylpenicillin. Kinetic studies revealed that degree of methylation of the CD molecule determines whether the CD has destabilizing or stabilizing effect on the β-lactam. The fully methylated βCD derivative Trimeb stabilizes benzylpenicillin while partial methylation of βCD only decreases to some extent the catalytic effect of native βCD. The complexes of all investigated CDs were also studied by DSC, FT-IR and NMR spectroscopy.