2426-02-0Relevant articles and documents
Protoporphyrinogen oxidase: High affinity tetrahydrophthalimide radioligand for the inhibitor/herbicide-binding site in mouse liver mitochondria
Birchfield, Norman B.,Casida, John E.
, p. 1135 - 1139 (1996)
Protoporphyrinogen oxidase (protox), the last common enzyme in heme and chlorophyll biosynthesis, is the target of several classes of herbicides acting as inhibitors in both plants and mammals. N-(4-Chloro-2-fluoro-5- (propargyloxy)phenyl)-3,4,5,6-tetrahydrophthalimide (a potent protox inhibitor referred to as THP) was synthesized as a candidate radioligand ([3H]-THP) by selective catalytic reduction of 3,6-dihydrophthalic anhydride (DHPA) with tritium gas followed by condensation in 45% yield with 4-chloro- 2-fluoro-5-(propargyloxy)aniline. Insertion of tritium at the 3 and 6 carbons of DHPA as well as the expected 4 and 5 carbons resulted in high specific activity [3H]THP (92 Ci/mmol). This radioligand undergoes rapid, specific, saturable, and reversible binding to the inhibitor/herbicide binding site of the protox component of cholate-solubilized mouse liver mitochondria with an apparent K(d) of 0.41 nM and B(max) of 0.40 pmol/mg of protein. In the standard assay, mouse preparation (150 μg of protein) and [3H]THP (0.5 nM) are incubated in 500 μL of phosphate buffer at pH 7.2 for 15 min at 25 °C followed by addition of ammonium sulfate and filtration with glass fiber filters. The potencies of five nitrodiphenyl ethers and two other herbicides as inhibitors of [3H]THP binding correlate well with those for inhibition of protox activity (r2 = 0.97, n = 7), thus validating the binding assay as relevant to enzyme inhibition. It is also suitable to determine in vivo block as illustrated by an ~50% decrease in [3H]THP binding in liver mitochondria from mice treated ip with oxyfluorfen at 4 mg/kg. This is the first report of a binding assay for protox in mammals. The high affinity and specific activity of [3H]THP facilitate quantitation of protox and therefore research on a sensitive inhibition site for porphyrin biosynthesis.
Crystal structure of 3,4,5,6-tetrahydrophthalic anhydride at 150 K
Ben Fredj, Arij,Bagieu-Beucher, Muriel,Ben Rejeb, Sadok,Ben Lakhdar, Zohra
, p. 1527 - 1535 (2004)
The crystal structure of 3,4,5,6-tetrahydrophthalic anhydride, (=4,5,6,7-tetrahydroisobenzofuran-1,3-dione; 1; C8H8O 3) was determined and refined by an analysis of three-dimensional X-ray-diffraction data at 150 K. This bicyclic compound crystallizes in space group Pbca with two symmetry-independent molecules I and II per asymmetric unit. The cyclohexene ring in both molecules adopts a half-chair conformation. The obtained conformational descriptions of the six-membered rings in the crystal phase are consistent with conformational data derived from molecular-orbital calculations. The structure analysis evidences considerable distorsion of the partially hydrogenated six-membered ring; the furan ring is flattened in molecule I and slightly deviated from planarity in molecule II. The short intermolecular distances found for C=O ... C=O are interpreted as evidence for nonbonded interactions of the dipole - dipole type. The rather long O ... H distances indicate that the C(sp3)-H ... O interactions are weak.
-
Shigemitsu
, p. 541 (1959)
-
Total synthesis of 6,7-dihydroligustilide
Li,Fang,Wang,Yang,Li
, p. 2051 - 2054 (1993)
A convenient, high yield total synthesis of 6,7-dihydroligustilide (1) is described starting from phthalic acid.
The profound effect of the ring size in the electrocyclic opening of cyclobutene-fused bicyclic systems
Ralph, Michael J.,Harrowven, David C.,Gaulier, Steven,Ng, Sean,Booker-Milburn, Kevin I.
supporting information, p. 1527 - 1531 (2015/01/30)
Fused cyclobutenes, prepared by the photocycloaddition of propargyl alcohols to cyclic anhydride chromophores, undergo facile thermochemical ring opening to fused γ-lactones. The size of the fused ring profoundly influences the temperature that is required to facilitate the ring opening (from 50°C to 180°C) and the nature of the product that is formed. Our studies provide new insights into the mechanistic course of these reactions and have been extended to facilitate the preparation of lactams fused to medium-sized rings.
Synthesis of chaetomellic anhydride A, A potent inhibitor of ras protein farnesyltransferase
Yoshimitsu, Takehiko,Arano, Yoshimasa,Kaji, Tomohiro,Ino, Tatsunori,Nagaoka, Hiroto,Tanaka, Tetsuaki
body text, p. 179 - 186 (2009/09/06)
Chaetomellic anhydride A, a potent inhibitor of Ras protein farnesyltransferase, was synthesized in 61% yield over four steps from methyl propionate. The synthesis features palladium-catalyzed carboxylation reaction under Cacchi conditions, efficiently in