HPLC method validation studies on a specific assay for monomethoxypoly(ethylene glycol) succinimido carbonate (mPEG-SC).

An UV-HPLC method for the determination of the potency of mPEG-SC, 5 kDa (1) has been developed and validated. Validation acceptance criteria that is typical of small molecule method validation was successfully applied for this method. The method relies on the HPLC separation of mPEG-OH, 5 kDa (2) and a derivatized form of mPEG-SC, 5 kDa (1).

Analytical method development for a specific assay method for monomethoxypoly(ethylene glycol)succinimido carbonate (mPEG-SC): A comparison of spectrophotometric, titrimetric and chromatographic methods.

Three different quantitative methods, which rely on base-mediated reactions for the purity assessment of the hydrolytically unstable activated ester, mPEG-SC (1) are discussed. In a spectrophotometric assay, controlled base-catalyzed hydrolysis of mPEG-SC (1) affords N-hydroxysuccinimide and its concentration can be determined by UV analysis. Reaction of mPEG-SC (1) with benzylamine and a non-aqueous back titration of the remaining benzylamine can also be used for purity determination of mPEG-SC (1).

The preparation of (1alpha,3beta)-3-hydroxycholestane-4,6-diene- 1,25-diol diacetate from a 5,7-diene precursor: a new method for the synthesis of heteroannular dienes.

Starting from the 7alpha-bromide 5a, a regioselective synthesis of (1alpha,3beta)-3-hydroxycholestane-4,6-diene-1,25-diol diacetate (2) is described. The preparative removal of contaminating 5,7-diene 9 was accomplished by the formation of the corresponding Diels-Alder adduct 11. Acetylation of the diacetate 2 followed by acid-catalyzed elimination and rearrangement yielded styrene 13.

gamma-Hydroxyalkynyl ketones as useful scaffolds for the preparation of combinatorial libraries of furans, isoxazoles and pyrazoles.

Using 5-hydroxy-hex-3-yne-2-one (9) as a model substrate, the utility of the gamma-hydroxyl alkynyl ketone scaffold for the preparation of combinatorial libraries of furans, isoxazoles, and pyrazoles is described. The addition of hydrazoic acid to the acetylenic ketone 9 forms in a single step both 3-azido-2,5-dimethyl furan (10) and alpha,5-dimethyl-3-isoxazolemethanol (11). Reaction of a mixture of (E)- and (Z)-bromoenediones (5 and 6), accessible from 3-bromo-2,5-dimethyl furan (17), with 1,1-dimethylhydrazine afforded a nearly quantitative yield of 1,3-dimethyl-5-acetylpyrazole (18).