CHEMISTRY OF SINGLET OXYGEN—XXV. PHOTOOXYGENATION OF METHIONINE*

Abstract— Methionine (Met) photooxidation sensitized by rose bengal has been studied as a function of pH and other variables. At pH ≤ 6, the reaction is a simple one, 2 Met + O₂→ 2 Methionine sulfoxide (MetO). At pH 6–10, another mechanism becomes important, leading to dehydromethionine; the structure of this compound was correctly assigned by Lavine (1945) as the heterocyclic N-S compound 2. One mole of H₂O₂ is also produced in this process. Dehydromethionine hydrolyzes slowly to MetO. Above pH9, a process leading directly to MetO + H₂O₂ becomes important. The stoichiometry of the latter two processes are Met + O₂+ H₂O → MetO + H₂O₂; competition among these three processes accounts for the puzzling variations in O₂ uptake. N-Formylated derivatives of methionine undergo only the first and third processes. Substantial catalytic effects of buffers complicate the picture. All the reactions appear to involve singlet oxygen, since there is the predicted effect of D₂O vs H₂O on the rate of reaction, although the situation is complicated by apparent aggregation of Met above 5 mM.     

Addition reactions of ROPHy/SOPHy oxime ethers: asymmetric synthesis of nitrogen containing compounds

Oxime ethers prepared from (R)- or (S)-O-(1-phenylbutyl)hydroxylamine (ROPHy or SOPHy) are versatile intermediates for the asymmetric synthesis of a range of nitrogen containing compounds including simple amines, 1,2-aminoalcohols, alpha- and beta-amino acids, heterocyclic building blocks of natural products, piperidine alkaloids, lactams, 5- to 8-membered ring nitrogen heterocycles, imino-sugars, and chiral ferrocene based receptors.     

A chemoenzymatic approach to glycopeptide antibiotics

Many biologically active natural products are constrained by macrocyclization and modified with carbohydrates. These two types of modifications are essential for their biological activities. Here we report a chemoenzymatic approach to make carbohydrate-modified cyclic peptide antibiotics. Using a thioesterase domain from the decapeptide tyrocidine synthetase, 13 head-to-tail cyclized tyrocidine derivatives were obtained with one to three propargylglycines incorporated at positions 3-8. These cyclic peptides were then conjugated to 21 azido sugars via copper(I)-catalyzed cycloaddition. Antibacterial and hemolytic assays showed that the two best glycopeptides, Tyc4PG-14 and Tyc4PG-15, have a 6-fold better therapeutic index than the natural tyrocidine. We believe this method will also be useful for modifying other natural products to search for new therapeutics.     

Interplanar torsion in the S1<--S0 electronic spectrum of jet cooled 1-phenylimidazole

The S(1)<--S(0) transition of 1-phenylimidazole (1PI) has been studied in a supersonic jet expansion by resonant two-photon ionization. The origin band at 36 075 cm(-1) is accompanied by a low frequency progression associated with torsion about the bond connecting phenyl and imidazole groups. Torsional potentials have been determined for both states. In S(0), phi(min)=37.2+/-0.5 degrees and the planar barrier is 339+/-20 cm(-1), while in S(1), phi(min)=17.6+/-0.5 degrees and the planar barrier is 57+/-2 cm(-1). The transition moment alignment is observed to be consistent with an excited state of L(b) character, in spite of the "off-axis" conjugation provided by the imidazole ring. These results are compared with ab initio calculations on both states, performed using Hartree-Fock, M?ller-Plesset second-order perturbation, density functional theory with the Becke3-Lee-Yang-Parr functional, time-dependent density functional theory, configuration interaction singles, and complete active space self-consistent field methods. Solution-phase UV spectra of neutral and protonated 1PI are also reported.     

Evidence for a monomeric structure of nonribosomal Peptide synthetases

Nonribosomal peptide synthetases (NRPS) are multimodular biocatalysts that bacteria and fungi use to assemble many complex peptides with broad biological activities. The same modular enzymatic assembly line principles are found in fatty acid synthases (FAS), polyketide synthases (PKS), and most recently in hybrid NRPS/PKS multienzymes. FAS as well as PKS are known to function as homodimeric enzyme complexes, raising the question of whether NRPS may also act as homodimers. To test this hypothesis, biophysical methods (size exclusion chromatography, analytical equilibrium ultracentrifugation, and chemical crosslinking) and biochemical methods (two-affinity-tag-system and complementation studies with enzymes being inactivated in different catalytic domains) were applied to NRPS subunits from the gramicidin S (GrsA-ATE), tyrocidine (TycB(1)-CAT and TycB(2-3)-AT.CATE), and enterobactin (EntF-CATTe) biosynthetic systems. These methods had revealed the dimeric structure of FAS and PKS previously, but all three NRPS systems investigated are functionally active as monomers.     

A copper-catalyzed C-N bond formation involving sp-hybridized carbons. A direct entry to chiral ynamides via N-alkynylation of amides

A copper-catalyzed new C-N bond formation involving a sp-hybridized carbon is described here leading to a facile entry for syntheses of chiral ynamides. This direct N-alkynylation of amides should have a significant impact on the future development of synthetic methodologies employing ynamides.     

Superoxide radical anion adduct of 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 2. The thermodynamics of decay and EPR spectral properties

The formation of the superoxide radical anion (O2*-) adduct of the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as detected by electron paramagnetic resonance (EPR) spectroscopy is one of the most common techniques for O2*- detection in chemical and biological systems. However, the nature of DMPO-O2H has confounded spin-trapping investigators over the years, since there has been no independently synthesized DMPO-O2H to date. A density functional theory (DFT) approach was used to predict the isotropic hyperfine coupling constants arising from the N, beta-H, and gamma-H nuclei of DMPO-O2H using explicit interactions with water molecules as well as via a bulk dielectric effect employing the polarizable continuum model (PCM). Theoretical calculation on the thermodynamics of DMPO-O2H decay shows favorable intramolecular rearrangement to form a nitrosoaldehyde and a hydroxyl radical as products, consistent with experimental observations. Some pathways for the bimolecular decomposition of DMPO-O2H and DMPO-OH have also been computed.     

Novel alkyl-modified anionic siloxanes as pseudostationary phases for electrokinetic chromatography. III. Performance in organic-modified buffers

Anionic water-soluble siloxanes modified with different amounts of alkyl chains have been used as pseudostationary phases in electrokinetic chromatography. Ionic siloxane polymers with attached alkyl chains of C8 and C12 and having different alkyl chain densities have been employed previously to achieve selective and efficient separations with a range of electrophoretic mobilities and methylene selectivities. In this study, the performance of three alkyl-modified siloxanes is examined in different organic-modified buffers and at differing amounts of organic modifier. The organic modifiers used are acetonitrile and methanol. The siloxanes are stable in these organic solvents and show good mobility and good methylene selectivities even at high concentration of organic solvent. Siloxanes have also been used to separate a mixture of 14 polynuclear aromatic hydrocarbons in an acetonitrile-modified buffer.     

Iron(II) and zinc(II) monohelical binaphthyl salen complexes

A new chiral binaphthyl salen ligand with rigid polyaromatic sidearms gives monohelical complexes (Fe(II) and Zn(II)) of predetermined handedness.     

Synthesis of the methanesulfonates of α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)emenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol,alpha styryl carbinol antifungal agents

The methanesulfonates of (α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol ( 1a, b ) are orally effective α-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile.