32819-24-2Relevant articles and documents
Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids
Ambro?ak, Agnieszka,Steinebach, Christian,Gardner, Erin R.,Beedie, Shaunna L.,Schnakenburg, Gregor,Figg, William D.,Gütschow, Michael
, p. 2621 - 2629 (2016/12/09)
The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses.
Pyrrolizidine alkaloid biosynthesis. Incorporation of 2-aminobutanoic acid labelled with 13C or 2H into the senecic acid portion of rosmarinine and senecionine
Stirling, Iain R.,Freer, Isabel K. A.,Robins, David J.
, p. 677 - 680 (2007/10/03)
(±)-[3,4-13C2]-2-Aminobutanoic acid 10 and (±)-[3,4-2H5]-2-aminobutanoic acid 11 are synthesized by alkylating diethyl acetamidomalonate with labelled ethyl iodide followed by acid hydrolysis. These compounds are used to obtain complete labelling patterns for the first time in a necic acid by studying the pyrrolizidine alkaloids rosmarinine 3 and senecionine 1 using NMR spectroscopy. The senecic acid portion 12 of both alkaloids shows equal incorporation of [3,4-13C2]-2-aminobutanoic acid 10 into the two C5 halves of the C10 acid consistent with formation of senecic acid via two molecules of isoleucine. After feeding [3,4-2H5]-2-aminobutanoic acid 11, retention of 2H at C-13 and C-20 of both alkaloids 13 confirms that the biosynthesis does not involve keto intermediates at these carbon atoms.
