Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A.

Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected formation of a 10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C. As a result, a thermodynamically stable structure was obtained. The structures of two new diastereomeric, unsaturated spiroketals, their configurations and conformations, were determined by means of NMR spectroscopy and molecular modelling. The reaction kinetics and mechanistic aspects of this transformation are discussed. These rearrangements provide a facile synthesis of novel macrolide scaffolds.

Novel 9a,11-bridged azalides: One-pot synthesis of N'-substituted 2-imino-1,3-oxazolidines condensed to an azalide aglycone.

An efficient one-pot method for the synthesis of novel 9a,11-bridged 15-membered 9a-aza-9-deoxo-9a-homoerythromycin A and its 6-O-methyl analogue has been developed. The novel bicyclic azalide scaffold is characterized by an N'-substituted-2-imino-1,3-oxazolidine moiety bound to a macrolactone ring between positions 9a and 11. Removal of the cladinose sugar from the starting compounds allows easy preparation of a small series of such bicyclic 3-keto and 3,6-hemiketal azalide derivatives. A mechanism for the formation of N'-substituted-2-imino-1,3-oxazolidines is discussed. Antibacterial properties of the prepared compounds were evaluated.

Synthesis and biological activity of 4''-O-acyl derivatives of 14- and 15-membered macrolides linked to omega-quinolone-carboxylic unit.

The synthesis and antimicrobial activity of a new class of macrolide antibiotics which consist of a macrolide scaffold and a quinolone unit covalently connected by an appropriate linker are described. Optimization of several synthetic steps and structural properties of lead compound 26 are discussed. Promising antibacterial properties of this compound and some of its analogues are reported.

ESI-MS studies of mixed-ligand Fe(II) complexes containing 1,10-phenanthroline and 1,10-phenanthroline-5,6-dione as ligands.

In order to monitor the progression of the synthesis and the separation of novel mixed-ligand iron complexes containing 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione, and NCS- as ligands all products were mass analyzed by electrospray ionization ion trap MS/MS. The spectra of methanol (MeOH), acetonitrile (ACN), water, and ethanol (EtOH) solutions were collected and the results were compared. It was detected under applied electrospray ionization mass spectrometry (ESI-MS) conditions that MeOH, water, and EtOH formed solvent clusters around the free or complexed 1,10-phenanthroline-5,6-dione. Owing to the solvent-ligand hydrogen-bond formation, the solvent-ligand clusters were formed in the polar protic solvents. The number of protic solvent molecules per complex ion in cluster depended on the number of 1,10-phenanthroline-5,6-dione ligands in the complex ion. Unlike MeOH, EtOH, or water, ACN was not involved in the formation of the solvent clusters with the iron complexes containing 1,10-phenanthroline-5,6-dione as ligand. We also showed that the NCS- group under certain solvent conditions served as a bidentate ligand.

ESI-MS studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives.

The aim of this report is to present the electrospray ionization mass spectrometry results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, 1-TsC, 1 and N-1-methanesulfonylcytosine, 1-MsC, 2 and their Cu(II) complexes Cu(1-TsC-N3)2 Cl2 , 3 and Cu(1-MsC-N3)2 Cl2 and 4 with biologically important cations: Na+ , K+ , Ca2+ , Mg2+ and Zn2+ . The formation of various complex metal ions was observed. The alkali metals Na+ and K+ formed clusters because of electrostatic interactions. Ca2+ and Mg2+ salts produced the tris ligand and mixed ligand complexes. The interaction of Zn2+ with 1-4 produced monometal and dimetal Zn2+ complexes as a result of the affinity of Zn2+ ions toward both O and N atoms. Copyright © 2016 John Wiley & Sons, Ltd.

Experimental and theoretical study of the cation binding properties of macrocyclic dehydrodibenzopyrido[15]annulenes.

The UV/Vis titration measurements, vibrational and NMR spectroscopy of isomeric dehydrodibenzopyrido[15]annulenes (DBPA) 1 and 2 clearly show that under proper conditions these macrocycles can achieve fast, quantitative and unselective binding of metal ions. The macrocycle 1 is an example of a hindered amine 2,6-bis(R)pyridine and its isomer 2 of a non-hindered amine 3,5-bis(R)pyridine. The protonation stoichiometry for both 1 and 2 was assumed to be DBPA:H(+)=1:1 and the formation constants logK=4.77±0.02 for 1, and logK=6.78±0.08 for 2 were obtained that well agree with those obtained under similar conditions for a macrocycle containing bipyridine units. The protonation of 2 gave the estimated stoichiometry of 2:H(+)=1:1 while the stoichiometric protonation of macrocycle 1 could not be achieved and the lower stability of the ion pair containing 1H(+) is most likely due to the inaccessibility of the nitrogen atom of 1 to the counterions and solvent molecules. The structures and electronic absorption spectra of 1 and 2, as well as the structures and spectra of 1H(+) and 2H(+), i.e. the species formed by protonation of the pyridine nitrogen, were calculated with the time-dependent DFT method with a B3LYP functional and a 6-31+G(d) basis set. The solvent effects were incorporated by means of the polarizable continuum model (PCM). The agreement of the calculated absorption data for the parent and protonated species with the observed spectra is rather satisfactory. Vibrational IR and Raman spectra of 1, 2, 1H(+) and 2H(+) in vacuo were calculated at the B3LYP/cc-pVTZ level of theory. Macrocycles 1 and 2, and their products protonated by trifluoromethanesulfonic acid (1HOTf and 2HOTf) were also characterized by temperature-dependent FTIR technique known as two dimensional IR correlation analysis. Quite large difference in degradation temperature between macrocycle 1 and 2 and their protonated complexes was measured, indicating that inclusion of proton leads to significant thermal stabilization of dehydroannulene ring.

Structural elucidation studies of 15-membered azalide macrocycles using H/D exchange and ESI-MS(n.).

A comprehensive study of fragmentation pathways of 15-membered azalide macrocycles using electrospray ionisation with multistage mass spectrometry (ESI-MS(n)) is presented in this work. Hydrogen/deuterium (H/D) exchange experiments and high-resolution mass spectrometry were used to investigate the proposed fragmentation pathways. In addition, the fragmentation patterns of sodium adduct ions [M+Na](+) of the macrocycles were also investigated as the presence of an alkali metal interacting with the aglycone ring influences the product-ion spectra.

ESI-MS studies of palladium (II) complexes with 1-(p-toluenesulfonyl)cytosine/cytosinato ligands.

The mononuclear complex Pd(1-TosC-N3)(2)Cl(2) (2) containing 1-(p-toluenesulfonyl)cytosine (1) as a ligand, as well as dinuclear complexes Pd(2)(1-TosC(-)-N3,N4)(4) (3) and Pd(2)(1-TosC(-)-N3,N4)(2)DMSO(2)Cl(2) (4) containing the ligand anion (1-TosC(-)), was mass analyzed by electrospray ionization ion trap MS/MS and high resolution MS. Complexes 3 and 4 were obtained by recrystallization of 2 from DMF and DMSO, respectively. The behavior of complex 2 in different solutions was monitored by electrospray ionization mass spectrometry (ESI-MS). Under the applied ESI-MS conditions, complex 2 in methanol reorganized itself dominantly as new complex 3 and the solvent did not coordinate the formed species. In H(2)O/DMSO, CH(3)CN/DMSO and CH(3)OH/DMSO solutions, complex 2 formed several new species with solvent molecules involved in their structure, e.g. complex 4 was formed as the major product. The newly formed species were also examined by LC-MS-DAD, confirming the solvent induced reorganization and the solution instability of complex 2.