Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones.

A remarkably concise, chromatography-free route to the parent compound of the paullone family of cyclin-dependent kinase (CDK) inhibitors is reported. A similar strategy allowed the synthesis of the hitherto missing 9-azapaullone and its protonated, N-oxidised and N-alkylated derivatives. Screening studies identified an active and strongly selective inhibitor of CDK9/cyclin T.

Intramolecular acylative ring-switching reactions of 3-(tetrahydro-2'-furyl)propanoic acid derivatives to give butanolides: mechanism and scope.

The mechanism by which dihydro-5-(3'-trifluoroacetoxypropyl)-2(3H)-furanone is formed when 3-(tetrahydro-2'-furyl)propanoic-trifluoroacetic mixed anhydride is treated with an acidic catalyst is defined, and routes to some potentially useful butanolide synthons are described.

Reactions of lithiated (E)-3-halo-1-phenylsulfonylprop-1-enes and (Z)-1-halo-3-phenylsulfonylprop-1-enes with aldehydes.

(E)-3-Chloro-1-phenylsulfonylprop-1-ene and its iodo- and bromo-analogues, (Z)-1-iodo-3-phenylsulfonylprop-1-ene and (Z)-1-bromo-3-phenylsulfonylprop-1-ene, have each been successfully converted into lithiated carbanions which react regioselectively with aromatic aldehydes to give gamma-alkylated products whose nature depends upon the halogen substituent: the chloro-sulfones yield (2Z)-1-aryl-2-chloro-4-phenylsulfonylbut-2-en-1-ols but the bromo- and iodo-derivatives behave differently, yielding (1E)-trans-4-aryl-3,4-epoxy-1-phenylsulfonylbut-1-enes. In sharp contrast, the same lithiated sulfones react with aliphatic aldehydes to give anti-configured beta-hydroxysulfones which are formed via diastereoselective alpha-alkylation reactions.

Impurities in a morphine sulfate drug product identified as 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine.

Stability testing of morphine sulfate formulated with nonpareil sugar seeds (consisting of sucrose and starch) and fumaric acid revealed the formation of the three impurities 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine. 5-(Hydroxymethyl)-2-furfural was isolated via semipreparative HPLC utilizing volatile mobile phase constituents and was identified by analysis of its HRMS and NMR spectra. 10-Hydroxymorphine and 10-oxomorphine were obtained via semipreparative HPLC and subsequent removal of ion-pair reagents using an anion exchange resin, or by solid phase extraction, and identified by spectroscopic analysis followed by comparison with authentic materials.