ABSTRACT
The direct inlet probe-electrospray ionization (DIP-ESI) presented here was based on the direct inlet probe-atmospheric pressure chemical ionization (DIP-APCI) developed by our group. It was coupled to an ion trap mass spectrometer (MS) for the detection of more polar compounds such as degradation products from pharmaceuticals. First, the position of the ESI tip, the gas and solvent flow rates, as well as the gas temperature were optimized with the help of the statistic program Minitab® 17 and a caffeine standard. The ability to perform quantitative analyses was also tested by using different concentrations of caffeine and camphor. Calibration curves with a quadratic calibration regression of R (2) = 0.9997 and 0.9998 for caffeine and camphor, respectively, were obtained. The limit of detection of 2.5 and 1.7 ng per injection for caffeine and camphor were determined, respectively. Furthermore, a solution of piracetam was used to compare established analytical methods for this drug and its impurities such as HPLC-diode array detector (DAD) and HPLC-ESI-MS with the DIP-APCI and the developed DIP-ESI. With HPLC-DAD and 10 µg piracetam on column, no impurity could be detected. With HPLC-ESI-MS, two impurities (A and B) were identified with only 4.6 µg piracetam on column, while with DIP-ESI, an amount of 1.6 µg piracetam was sufficient. In the case of the DIP-ESI measurements, all detected impurities could be identified by MS/MS studies. Graphical Abstract Scheme of the DIP-ESI principle.
Subject(s)
Chromatography, High Pressure Liquid/methods , Piracetam/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methodsABSTRACT
A 3,4-O-unprotected galactal derivative having bulky 6-O-TIPS protection (compound 2) could be regioselectively 3-O-glycosylated with O-(galactopyranosyl) trichloroacetimidates; depending on the protecting group pattern stereoselectively alpha- and beta-linked disaccharides were obtained. With O-(2-azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A), glycosylation of 2 and of a 6-O-unprotected galactal derivative led in acetonitrile as solvent exclusively to a beta(1-3)- and a beta(1-6)-linked disaccharide, respectively. Nitration of the galactal moieties of the saccharides followed by Michael-type addition of serine and threonine derivatives (7a,b) installed the alpha-galacto-configuration, thus readily furnishing O-glycosyl amino acid building blocks for the incorporation of core 1, core 2, core 3, core 6, and core 8 structures into glycopeptides. 2-Nitrogalactal and 2-nitroglucal derivatives could be also successfully employed in glycoside bond formation via Michael-type addition in a reiterative manner, affording the corresponding core 5, core 7, and core 6 building blocks. In this approach, highly stereoselective glycoside bond formations were based exclusively on Michael-type addition to the nitro-enol ether moiety of the 2-nitroglycals. Hence, 2-nitroglycals are versatile intermediates for base-catalyzed glycoside bond formation.
Subject(s)
Galactose/analogs & derivatives , Glycosides/chemical synthesis , Mucins/chemical synthesis , Antigens, Tumor-Associated, Carbohydrate/chemistry , Carbohydrate Sequence , Galactose/chemical synthesis , Galactose/chemistry , Glycosides/chemistry , Glycosylation , Molecular Sequence DataABSTRACT
Base-catalyzed glycosylations provide the basis for a new and general entry to the synthesis of mucin-type O-glycans. The desired α-linked 2-acetamidoglycosyl amino acids B are accessible selectively starting from glycals of type A. Fmoc=9-fluorenylmethoxycarbonyl.
