Richard H. Cox

Synthesis and characterization of 4-dimethylamino-N-triphenylmethylpyridinium chloride, a postulated intermediate in the tritylation of alcohols

Abstract 4-Dimethylamino- N -triphenylmethylpyridinium chloride ( 1 ) reacts with primary but not secondary alcohols to produce trityl ethers in good yield; in addition, amines may be selectively N - tritylated witth 1 in the presence of alcohols.

Regiospecificity and stereospecificity in the enzymatic conjugation of glutathione with (±)-benzo(a)pyrene 4,5-oxide

Abstract 13 C-NMR analysis of the glutathione conjugates formed from (±)-benzo(a)-pyrene 4,5-oxide-4,5- 13 C by a purified glytathione transferase from little skate ( Raja erinacea ) liver demonstrated that equivalent amounts of the positional isomers (4,5-dihydro-4-hydroxy-5-glutathionylbenzo(a)pyrene and 4,5-dihydro-4-glutathionyl-5-hydroxybenzo(a)pyrene) were formed. Separation of these conjugates by HPLC and subsequent 13 C-NME studies showed that only one diastereoisomer of each positional isomer was formed by the skate enzyme, each enantiomer of the arene oxide having produced only one of the two possible positional isomers. The non-enzymic reaction of (±)-benzo(a)pyrene 4,5-oxide with glutathione produced the four possible stereoisomers resulting from trans addition to the epoxide ring. This was also true when rat liver cytosol was used as the source of transferase activity. The data demonstrate that skate liver glutathione transferase 4 has high substrate regiospecificity and stereospecificity for (±)-benzo(a)pyrene 4,5-oxide.

Synthesis and relative stereochemistry of the four mercapturic acids derived from styrene oxide and N-acetylcysteine.

The chemical reaction between (+/-)-styrene oxide and N-acetylcysteine produces both positional isomers (1 and 2) as a mixture of diastereoisomers with a preference for the benzylic thioether isomer 1 (2 : 1). Synthesis of the mercapturic acid conjugates from either (+)- or (-)-styrene oxide produces only two of the four possible stereoisomers. The single diastereoisomers of 1 and 2 were separated by high pressure liquid chromatography (HPLC) and identified by 1H- and 13C-nuclear magnetic resonance (NMR). The relative stereochemistry at the benzylic carbon center of the mercapturic acid conjugates was assigned on the basis of the established chemical correlation between optically pure styrene oxide and its precursor mandelic acid, and considerations on the mechanism of ring opening of epoxides by sulfur nucleophiles. The stereochemical definition of the isomers 3-6 should prove useful in investigations of the biotransformation of the glutathione (GSH) conjugates of styrene oxide.

Isolation and identification of two new biologically active norditerpene dilactones from Aspergillus wentii

Abstract Two new biologically-active norditerpenoid dilactones were purified from culture extracts of Aspergillus wentii and assigned the trivial names wentilactone A and wentilactone B. The absolute chemical structure of wentilactone A was determined by single crystal X-ray diffraction and circular dichroism. The structure of wentilactone B was determined by 1 H and 13 C NMR analyses. Wentilactone A had an ld 50 of 7.0 mg/kg when administered orally to 1-day-old chickens. Both metabolites inhibited growth in wheat coleoptile bioassays.

Synthesis and relative stereochemistry of the benzylic thioether diastereoisomers formed from glutathione and styrene oxide

Abstract The chemical reaction between (±) styrene oxide and glutathione produces both the benzylic and primary thioether positional isomers as a mixture of diastereoisomers ( 2, 5 and 3, 6 ), with a preference for the benzylic thioether isomers (66 : 34). Synthesis of the styrene oxide-glutathione conjugates from either (+)- or (−)- styrene oxide produces both positional isomers as single diastereoisomers. The benzylic thioether isomers ( 2 and 5 ) were prepared from protected 2-bromo-2-phenylethanol ( 8 ) and glutathione and were separated using hplc. The relative stereochemistry of the benzylic thioether isomers was assigned on the basis of the established chemical correlation between the optically pure styrene oxides and their precursors, the mandelic acids, as well as considerations of the mechanism of ring opening of epoxides by sulfur nucleophiles. The availability of the single diastereoisomers of the benzylic thioether isomers and the styrene oxideglutathione conjugates enables investigations concerned with the influence of chirality on the biotransformation and excretion of these conjugates.

Aflatoxin B1S: Revised Structure for the Sodium Sulfonate Formed by Destruction of Aflatoxin B1 with Sodium Bisulfite1,2

A promising method for the destruction of aflatoxin B1 in commodities is treatment with sodium bisulfite to yield a single major product, aflatoxin B1S. On the basis of nuclear magnetic resonance, ultraviolet and infrared spectra, elemental analysis, mass spectroscopy, deuterium labeling and stability to highly acidic conditions, the structure of aflatoxin B1S was established as the 15 α-sodium sulfonate of aflatoxin B1 The formation of aflatoxin B1 products substituted at the 15 position only is unprecedented and implies an unusual mechanism. The formation of a single trans addition product under conditions that seemingly rule out a previously proposed free radical mechanism suggested a newly proposed ionic reaction mechanism. The completeness of the reaction and the water solubility of aflatoxin B1S support the promising use of bisulfite to destroy aflatoxin.

The structure of chaetoglobosin K.

Abstract The structure of chaetoglobosin K, a toxic metabolite from Diplodia macrospora , has been determined by single crystal X-ray analysis.

HPLC Analysis of the Isomeric Thioether Metabolites of Styrene Oxide

Abstract An efficient separation of the isomeric thioether metabolites of styrene oxide was achieved under reversed-phase conditions. The column was eluted isocratically with 15% methanol in buffered solutions of phosphoric acid-tris-hydroxymethylaminomethane. The thioether conjugates were separated by class, and the order of elution was cysteine, cysteinylglycine, glutathione, and N-acetylcysteine. The effect of pH and buffer salt concentration on the HPLC separation was examined. Optimal conditions for a separation were either found at low pH (pH 3 or 4) or neutral pH, both at a high buffer salt concentration (75mM). The positional isomers and stereoisomers comprising each amino acid conjugate sample were separated into two peaks. The variations in k1 and α observed with changes in pH were interpreted as reflecting the degree of interaction of the ionizable groups in the amino acid residue and the hydrophobic portion of the molecule. This interaction was found to be strongly influenced by the relative s...

Isolation and structural elucidation of a novel sterol metabolite of Fusarium sporotrichioides 921

The isolation and identification of 12β-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-3β,11α-diol (3) from Fusarium sporotrichioides 921, previously associated with a fatal outbreak of alimentary toxic aleukia, is described.