Determination of degradation products of squalamine lactate using LC/MS.

Heat, acid and base stress methods were applied to study the stability of squalamine lactate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identifications were assigned based on their molecular weight measurements, reactivity and MS/MS fragmentation. Solid squalamine lactate generated a new amide, namely lactyl squalamide, when heated to 80 degrees C. Chemical structure for this new compound has been established by NMR and MS data interpretation and confirmed by direct comparison between the degradant and the synthesized compound. Squalamine lactate in pH 4 acetate buffer solution produced more degradants under stressed conditions. These degradants are formed due to the loss of the sulfate functionality. Squalamine lactate is stable in refrigerated conditions as well as in basic solution.

An unusual course of thioglycoside activation with bromine: synthesis and crystal structure of 4-O-acetyl-2-bromo-2,3,6-trideoxy-3-C-methyl-3-trifluroacetamido-alpha-L-altropyranosyl bromide.

Bromine activation of phenyl 4-O-acetyl-2,3,6-trideoxy-3-C-methyl-3-trifluoroacetamido-1-thio-alpha,beta-L-ribo-hexopyranoside and attempted coupling with an acceptor in the presence of silver silicate gave an unusual bicyclic product, 2-trifluoromethyl-(4-O-acetyl-2-bromo-2,3,6-trideoxy-3-C-methyl-alpha-L-altrohexopyrano)-[3,2,1-d,e]-2-oxazine, instead of the expected disaccharide. Detailed investigation supported by X-ray crystallographic analysis showed that a trans dibromide is an intermediate in this reaction and that the dibromide is likely formed from a glycal that is generated by elimination during the coupling step.