Oxidation of the side chains of ergosterol derivatives

Summary The acetate of bisnorlithocholic acid has been obtained with a yield of 65% from the acetate of 5-ergost-22-en-3-ol by permanganate-periodate oxidation.S. Ordzhonikidze All-Union Scientific-Research Institute of Pharmaceutical Chemistry, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 88–91, January–February, 1978.     

Semiempirical study of the conformation of tetroxane and its halogenated derivatives

We have made a conformational study of tetroxane and its bi- and tetra-halogenated derivatives by means of the semiempirical AM1 and PM3 molecular orbital methods. The results are compared with previous semiempirical and ab initio studies as well as with available experimental data. We have found that in every case the AM1 method underestimates the peroxidic O-O bond length by approximately 12%, while the PM3 procedure describes such a bond in a better way. The degree of accuracy of these two semiempirical methods is discussed in relation with the tetroxane structure.     

X-Ray diffraction study of the new ecdysteroid derivatives containing isoxazoline ring in the side chain

Crystal and molecular structure of (2β,3β,14α,20R,5′R)-14,20-dihydroxy-20-(3′-isopropylisoxazolin-5′-yl)-2,3-isopropylidenedioxy-5β-pregn-7-en-6-one and (2β,3β,14α,20R,5′R)-20-hydroxy-20-(3′-methylisoxazolin-5′-yl)-14-trimethylsilyloxy-2,3-isopropylidenedioxy-5β-pregn-7-en-6-one was investigated by XRD analysis. Compounds crystallize in the orthorhombic [space group P2₁2₁2₁; a 1.751(2), b 12.146(2), c 19.660(4) Å] and hexagonal [space group P6₁; a 14.138(3), b 14.138(3), c 27.597(7) Å] crystal systems, respectively. These compounds, which resulted from the 1,3-dipolar cycloaddition of isobutyronitrile oxide or acetonitrile oxide to the corresponding steroid olefin, have 5′R-stereochemistry of the formed chiral center. The conformation of the side chain of molecules is stable due to the intramolecular hydrogen bonds.     

A deuteron NMR study of axial motion and side chain conformation in the mesophase of discotic liquid crystal main-chain polymers

Pulsed deuteron NMR spectroscopy has been used to examine the axial motion and the side-chain conformation in both oriented and unoriented mesophases of discotic liquid crystal main-chain polymers based on pentyloxy or heptyloxy substituted triphenylenes. Lineshape simulations show that the rotational motion of the triphenylene rings about the column axes can be described by an inhomogeneous distribution of reorientation angles around 45°. However, only about 60% of the discs are involved in such large amplitude motions; the remaining 40% have reorientation angles below 10°. This illustrates the severe restrictions imposed on the rotation of the discs by the interlinkage of the columns via the alkylene spacers. Furthermore, the simulations demonstrate that, at the -carbon, the side chains show very little fast internal motion, but have a relatively complex conformation involving a disorder which does not change on the microsecond timescale. Since such a disorder is not present in the corresponding monomeric samples it is ascribed to the presence of the spacers. These results are also consistent with the presence of large sterical hindrances between the first side chains segments of adjacent discs, and they indicate a correlated reorientation of the discotic units within a column.     

Proton NMR study of molecular motion in polydimethylsiloxane

Proton spin–lattice relaxation times T₁ were measured for two samples of polydimethylsiloxane (PDMS), one with weight-average molecular weight M_w = 77,400 and the other with M_w = 609,000. Two T₁ minima and a T₁ discontinuity were observed for each compound. The high-temperature T₁ minima were attributed to a stretching and flexing motion of the PDMS chain. Quantitative comparison of the relaxation data with a theoretical model developed for this motion allowed the activation energy, 2.3 kcal/mole, and the maximum angular displacement of the methyl group symmetry axis to be determined. The latter was found to be 31°, independent of sample molecular weight. The low-temperature minima were ascribed to methyl reorientation with an activation energy of 1.6 kcal/mole. The T₁ discontinuities were attributed to melting and allowed the degree of crystallinity to be estimated.     

Liquid crystallinity of newly synthesized glucose derivatives with mesogenic side chains

Synthesis of glucose derivatives by direct esterification of the five available sites on D-(+)-glucose with side chains containing a biphenyl mesogenic moiety, a pentyl spacer and an alkyl tail is reported for the first time. Liquid crystalline phase behaviour of these glucose derivatives was studied by optical microscopy, thermal and X-ray diffraction methods. A layered arrangement of the smectic A (SmA) type was commonly observed in the above materials. An increase in the length of the alkyl tail results in a change of the phase structure from smectic Ai(SmAi), intercalated layer phase, to smectic As(SmAs), segregated bilayer phase. From the transition temperature and enthalpy observations, the SmAs phase has higher order than the SmAi phase. Cholesteric and chiral smectic C phases were also observed in addition to the SmA for some of the glucose derivatives, demonstrating a potential for preparing chiral liquid crystals.     

Biomolecular NMR using a microcoil NMR probe--new technique for the chemical shift assignment of aromatic side chains in proteins

A specially designed microcoil probe for use in biomolecular NMR spectroscopy is presented. The microcoil probe shows a mass-based sensitivity increase of a minimal factor of 7.5, allowing for the first time routine biomolecular NMR spectroscopy with microgram amounts of proteins. In addition, the exceptional radio frequency capabilities of this probe allowed us to record an aliphatic-aromatic HCCH-TOCSY spectrum for the first time. Using this spectrum, the side chains of aliphatic and aromatic amino acids can be completely assigned using only a single experiment. Using the conserved hypothetical protein TM0979 from Thermotoga maritima, we demonstrate the capabilities of this microcoil NMR probe to completely pursue the sequence specific backbone assignment with less than 500 microg of (13)C,(15)N labeled protein.     

Proton affinity ladder for uridine and analogs: influence of the hydroxyl group on the sugar ring conformation

A ladder of relative proton affinities (PA) for a series of modified uridines (e.g. araU, ddU, 5BrU, 5BrdU and 5IU) was established from competitive dissociations of proton-bound heterodimers using Cooks and co-workers' kinetic method. The studied heterodimers are constituted of a modified nucleoside and either an amino acid or a nucleoside with known PA value. These non-covalent heterodimers were prepared under electrospray conditions to be selected and dissociated into the ion-trap analyzer. These results allowed our PA ladder of uridine and deoxyuridine analogs substituted at the C-5 position in the uracil ring to be extended. From this scale, it was showed that the substitution of hydrogen atom at the C-2' position in the sugar ring by a hydroxyl group involves a decrease of about 7 kJ mol(-1). The experimental values for U, 5MeU, dU, 5MedU, ddU and araU are consistent with those obtained by DFT calculations (B3P86/6-31+G//B3LYP/6-31G(.)). Several neutral and protonated conformations of these compounds were considered, in particular the ring conformation of furanose and the orientation of the base with respect to the sugar ring. These calculated results showed the influence of sugar substituent on the conformation of the neutral form of theses nucleosides. However, the most stable protonated structure is the same for all the studied nucleosides except for araU, where the position of the anti 2'-OH group imposes a specific conformation.     

Proton transfer in the hydrogen-bonded chains of lepidocrocite: a computational study

A responsible approach to the development of alternative energy sources, storage and conversion systems is to utilize abundant materials, with minimal or no negative environmental impacts. Here we report that lepidocrocite (γ-FeOOH, a naturally occurring metastable phase of iron oxyhydroxide) shows great promise as a proton conductor, based on sophisticated first-principles calculations that include the important corrections of on-site Coulomb interactions for this strongly correlated material. Our results show how proton transfer is facilitated by phonon vibration modes and relatively low transition energy barriers.     

Helical stacking tuned by alkoxy side chains in pi-conjugated triphenylbenzene discotic derivatives

We report on the synthesis and self-assembly of a new series of discotic molecules containing triphenylbenzene as the core and alkoxy side chain with varying length. It was found that compounds 3 a-c, 4 b and 5 b could form stable gels in several apolar solvents. Transmission electron microscopy (TEM) images revealed that their morphologies were very different for the different alkoxy-substituted organogels. In toluene or hexane, 3 b and 3 c resulted in both left- and right-handed helical fibers, whereas 3 a resulted in straight rigid fibers; 4 b and 5 b resulted in most straight fibers with a few twisted fibers. The results from FT-IR and UV/Vis absorption spectroscopy indicated that the hydrogen bonding and pi-pi interactions were the main driving forces for the formation of the self-assembled gels. Further detailed analysis of their aggregation modes were conducted by UV-visible absorption spectra and X-ray diffraction (XRD) measurements. Based on these findings, the influence of these peripheral alkoxy substituents on the gel formation and the aggregation mode were discussed. The special enhanced fluorescent emissions, which resulted from aggregation, were also found in the gel phase.     

GC-MS analysis of acylated derivatives of the side chain and ring regioisomers of methylenedioxymethamphetamine

The perfluoroacyl derivatives (pentafluoropropionylamides and heptafluorobutrylamides) of the primary and secondary regioisomeric amines, related to the controlled drug substance 3,4-methylenedioxymethamphetamine, are prepared and evaluated in GC-MS studies. These derivatives show excellent resolution on nonpolar stationary phases, such as RTX-1 and RTX-5, with elution order differences from those of the underivatized amines. The mass spectra for these derivatives are significantly individualized, and the resulting unique fragment ions allow for specific side-chain identification. The individualization is the result of fragmentation of the alkyl carbon-nitrogen bond, yielding hydrocarbon fragments and other unique ions. The heptafluoro butrylamides derivatives offer more fragment ions for molecular individualization among these regioisomeric substances.     

Proton exchange in 1-vinyl-1,2,4-triazole and its derivatives

Proton exchange at C(₅) of the triazole ring has been studied in 1-vinyl-1,2,4-triazole, 1-ethyl-1,2,4-triazole, poly-1-vinyl-1,2,4-triazole, and their quaternary salts. The rate of exchange is catalyzed by bases and inhibited by acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1365–1368, October, 1987.     

Synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives with amphoteric side chains

Novel benzamide derivatives (19-24, 32a-c, 43d-f), each possessing a cycloaminoalkanecarboxylic acid side chain, were synthesized and their gastrointestinal prokinetic and dopamine D2 receptor antagonist activities were evaluated. 4-[(4-Amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetic acid (19) exhibited the most potent gastro- and colon-prokinetic activities, through intravenous administration to conscious dogs, and also showed the reduced dopamine D2 receptor antagonistic activity. However, 19 showed only weak gastrointestinal prokinetic activity after oral administration. Several ester prodrugs (44-62) of 19 were tested for pharmacological activities as well as physicochemical and metabolic stability; the butyl ester (46) was consequently selected as a promising gastrointestinal prokinetic agent with reduced side effects.     

Biosynthetic 13C labeling of aromatic side chains in proteins for NMR relaxation measurements

Site-specific 13C labeling offers a desirable means of eliminating unwanted relaxation pathways and coherent magnetization transfer in NMR relaxation experiments. Here we use [1-13C]-glucose as the sole carbon source in the growth media for protein overexpression in Escherichia coli. The approach results in specific incorporation of 13C at isolated positions in the side chains of aromatic amino acids, which greatly simplifies the measurements and interpretation of 13C relaxation rates in these spin systems. The method is well suited for characterization of chemical exchange by CPMG or spin-lock relaxation methods. We validated the method by acquiring 13C rotating-frame relaxation dispersion data on the E140Q mutant of the C-terminal domain of calmodulin, which reveal conformational exchange dynamics with a time constant of 71 mus for Y138.     

Synthesis of polyesters containing nucleic acid base derivatives as pending side chains

Preparations of four diol monomers containing nucleic acid bases and the corresponding model polymers of polynucleotides with linear polyester backbone and nucleic acid base derivative as pending side chains are described. N-(1′,3′-Dihydroxy-2′-methyl-2′-propyl)-2-(thymin-l-yl)propionamide ( Ia , HMPTPA), N-(1′,3′-dihydroxy-2-methyl-2′-propyl)-2-(uracil-l-yl)propionamide ( Ib , HMPUPA), and their isomers, N-(β,β′-dihydroxyethyl)-2-(thynin-1-yl)propionamide ( IIa , HETPA) and N-(β,β′-dihydroxyethyl)-2-(uracil-1-yl)propionamide ( IIb , HEUPA) were synthesized through the selective N-acylation of 2-methyl-2-amino-1,3-propanediol and diethanolamine with 2-(thymin-1-yl)propionic acid (TPA) and 2-(uracil-1-yl)propionic acid (UPA), respectively, by the active amide-benzotriazole method. Diol monomers I and II were polycondenzed with active amide of benzotriazole such as 1,1′-(isophthaloyl)bisbenzotriazole (IPBBT) in the presence of triethylamine and in DMF at 60°C, giving polyesters containing thymine and uracil derivatives as the side group. Prior to polymer synthesis, an O-acylation of Ia using the active monoamide l-benzoylbenzotriazole was carried out as a model compound study.     

The assignment of the 1H NMR signals to the methine bridge H-atoms in chlorophyll derivatives

Experiments are described which prove the assignments of the α- and β-protons in the ¹H NMR spectra of methyl phaeophorbide a ( 1 ) and methyl pyrophaeophorbide a ( 2 ). Because of the structural relationship between derivatives of the bacteriochlorophylls d ( 5 ) and 2 , dehydration of 5 results in a homologue mixture [2-(des-α-hydroxyethyl)-2-vinyl-bacteriomethyl phaeophorbide] d ( 6 ) of 2. Since the homologue substituents in 6 are located at C-4 and C-5 surrounding the β-H position, and since only one broad signal appears in its ¹H NMR spectrum, this is assigned to the β-proton. This experiment proves that the sequence of increasing shielding is β, α and δ in 6 ; and, therefore, the same sequence applies to the ¹H NMR spectra of 1 and 2 . This knowledge reveals that the product of electrochemical reduction of 1 in deuteromethanol is exclusively an α-chlorin-phlorin ( 8 ). In addition, the ¹H NMR spectrum of the 2-vinyl derivatives of the bacteriomethyl phaeophorbides c ( 7 ) shows the same broad signal at lowest field as does that of 6 . The sequence of increasing shielding is therefore, β, α. The influence of the additional δ-methyl group in 7 on the ring current is explained.     

NMR and X-ray study of cyclotetraveratrilene derivatives

A conformational study of cycloveratrilenes 3 and 4 by high resolution NMR at low temperature for 3 and room temperature for 4 along with X-ray crystallography is reported. From these experiments we found a dynamic process, where magnetic and topologic environment are exchanged by conformational variations through rotations. A conformational study of two cyclotetraveratrilenes by high resolution NMR at low and room temperature along with X-ray crystallography is reported. From these experiments we found a dynamic process, where magnetic and topologic environment are exchanged by conformational variations through rotations.     

Selective D ring side chain tritiation of steroidal natural products

This paper describes the tritiation of several steroid natural products at their D ring side chain, taking advantage of selective catalytic tritium reductions.