The design of efficient and selective routes to a key 1,4-cis-substituted cyclohexylamide intermediate

This Letter describes the synthetic challenges in synthesising key 1,4-cis-substituted cyclohexylamide intermediate 1 for our research programme. Five different routes address the major issues of selectivity to afford the cis product in isomerically pure form and in high yield. Major purification issues were also encountered upon scaling some of the routes. The merits of the diverse routes are assessed and the reasoning given for which one was ultimately used for large-scale synthesis of 1.     

Novel guanosine-cytidine dinucleoside that self-assembles into a trimeric supramolecule

[reaction: see text] Synthesis and assembly studies of a guanosine-cytidine dinucleoside 1 that self-assembles into a trimeric supramolecule (I) are presented. Dinucleoside 1 was obtained by utilizing two consecutive palladium-catalyzed cross-coupling reactions. Ensemble I was analyzed by ESI-MS, NMR spectroscopies, size exclusion chromatography (SEC), and vapor pressure osmometry (VPO).     

Robust mixed 10/12 helices promoted by "alternating chirality" in a new family of C-linked carbo-beta-peptides

The C-linked carbo-beta-peptides, oligomers of a new class of C-linked carbo-beta3-amino acids, have been shown to generate mixed 12/10 and 10/12 helices. The design involves use of "alternating chirality" of the epimeric (at the amine center) monomers to control the stability of these helices. The observation of stable 12/10 helix in a tripeptide and 10/12 helix in a tetrapeptide is unprecedented.     

Two new macrocyclic diaryl ether heptanoids from Boswellia ovalifoliolata

The stems of Boswellia ovalifoliolata BAL. & HENRY (Burseraceae) afforded two new macrocyclic diaryl ether heptanoids, ovalifoliolatin A (1) and B (2) together with three known compounds; acerogenin C (3), 3 alpha-hydroxyurs-12-ene (4), and sitost-4-en-3-one (5). The structures were established by means of spectroscopic analysis and compounds 1, 3-5 were evaluated for their antibacterial activity.     

Mass spectral study of alkali-cationized Boc-carbo-beta3-peptides by electrospray tandem mass spectrometry

Electrospray tandem mass spectrometry was used to study the dissociation reactions of [M+Cat]+ (Cat = Na+ and Li+) of Boc-carbo-beta3-peptides. The collision-induced dissociation (CID) spectra of [M+Cat-Boc]+ of these peptides are found to be significantly different from those of [M+H-Boc]+ ions. The spectra are more informative and display both C- and N-terminus metallated ions in addition to characteristic fragment ions of the carbohydrate moiety. Based on the fragmentations observed in the CID spectra of the [M+Cat-Boc]+ ions, it is suggested that the dissociation involves complexes in which the metal ion is coordinated in a multidentate arrangement involving the carbonyl oxygen atoms. The CID spectra of [M+Cat-Boc]+ ions of the peptide acids show an abundant N-terminal rearrangement ion [b(n)+17+Cat]+ which is absent for esters. Further, two pairs of positionally isomeric Boc-carbo-beta3-peptide acids, Boc-NH-Caa(S)-beta-hGly-OH (11) and Boc-NH-beta-hGly-Caa(S)-OH (12), and [Boc-NH-Caa(S)-beta-hGly-Caa(S)-beta-hGly-OH] (13) and [Boc-NH-beta-hGly-Caa(S)-beta-hGly-Caa(S)-OH] (14), were differentiated by the CID of [M+Cat-Boc]+ ions. The CID spectra of compounds 11 and 13 are significantly different from those of 12 and 14, respectively. The abundance of [b(n)+17+Cat]+ ions is higher for peptide acids 12 and 14 with a sugar group at the C-terminus when compared to 11 and 13 which contain a sugar moiety at the N-terminus. The observed differences between the CID spectra of these isomeric peptides are attributed to the difference in the preferential site of metal ion binding and also on the structure of the cyclic intermediate involved in the formation of the rearrangement ion.     

A Validated chiral LC Method for the Enantiomeric Separation of Galantamine

A rapid isocratic chiral HPLC method has been developed for the separation of R-galantamine from S-galantamine. Good resolution viz. Rs > 3 between R- and S- forms of galantamine was achieved with chiralpak AD-H (250 × 4.6 mm) column using n-hexane, 20% propionic acid in isopropanol and diethyl amine in the ratio of 80:20:0.2 (v/v) as mobile phase at ambient temperature. Flow rate was kept as 0.8 mL min⁻¹ and the elution was monitored at 289 nm. This method was further used to determine the amount of R-galantamine in pure and pharmaceutical formulations of S-galantamine. This method is capable to detect and quantitate R-galantamine to the levels of 0.21 and 0.84 μg mL⁻¹, respectively. The method was validated as per International Conference on Harmonization (ICH) guidelines in terms of limit of detection (LOD), limit of quantification (LOQ), linearity, precision, accuracy, specificity, robustness and ruggedness.     

Synthesis and magnetic properties of NiFe2−xAlxO4 nanoparticles

Nanocrystalline Al-doped nickel ferrite powders have been synthesized by sol–gel auto-ignition method and the effect of non-magnetic aluminum content on the structural and magnetic properties has been studied. The X-ray diffraction (XRD) revealed that the powders obtained are single phase with inverse spinel structure. The calculated grain sizes from XRD data have been verified using transmission electron microscopy (TEM). TEM photographs show that the powders consist of nanometer-sized grains. It was observed that the characteristic grain size decreases from 29 to 6 nm as the non-magnetic Al content increases, which was attributed to the influence of non-magnetic Al concentration on the grain size. Magnetic hysteresis loops were measured at room temperature with a maximum applied magnetic field of ≈1 T. As aluminum content increases, the measured magnetic hysteresis curves become more and more narrow and the saturation magnetization and remanent magnetization both decreased. The reduction of magnetization compared to bulk is a consequence of spin non-collinearity. Further reduction of magnetization with increase of aluminum content is caused by non-magnetic Al³⁺ ions and weakened interaction between sublattices. This, as well as the decrease in hysteresis was understood in terms of the decrease in particle size.     

Functionalized base-pairs: versatile scaffolds for self-assembly

This article discusses the development of synthetic supramolecular systems derived from hydrogen bond driven base-pairing, with a focus on the self-assembly of individual nucleobase analogues.     

T1rho-weighted MRI using a surface coil to transmit spin-lock pulses

T1rho-weighted MRI is a novel basis for generating tissue contrast. However, it suffers from sensitivity to B1 inhomogeneity. First, excitation with a spatially varying B1 causes flip-angle artifacts and second, spin locking with an inhomogeneous B1 results in non-uniform T1rho contrast. In this study, we overcome the former complication with a specially designed spin-locking pulse sequence and we successfully obtain T1rho-weighted images with a surface coil. In this pulse sequence, the spin-lock pulse was divided into segments of equal duration and alternating phase. This "self-compensating" T1rho-preparatory pulse sequence was analyzed and the effect of an inhomogeneous B1 field was simulated using the Bloch equations. T1rho-weighted MR images of a phantom and a human knee joint in vivo were obtained on a clinical scanner with a surface coil to demonstrate the utility of the pulse sequence. The self-compensating T1rho-prepared pulses sequence resulted in substantially reduced image artifacts compared to the conventional, single-phase spin-lock pulse.     

Enhancing Hoogsteen interactions: a pyrrole-containing purine nucleoside that competes with guanosine self-assembly

A pyrrole-appended purine nucleoside 1 is described that can form an "extended" three-point Hoogsteen-type interaction due to the stabilization of the donor-acceptor-acceptor (DAA) motif. Nucleoside 1 is shown to bind guanosine 10 (a classic ADD motif) to form ensemble I. This interaction competes effectively with guanosine self-assembly and, as such, is capable of disrupting guanosine quadruplex formation.