Synthesis of penicillin analogs, (--)-methyl 6-epi-6-bromobisnorpenicillanate and (+/-)-methyl 6-epi-bromopenicillanate.

The [(4-methoxycarbonylthiazolidino)carbonyl-dihalomethyl]phenylmercury compounds 2a,b and 5a,b have been synthesized. When heated in refluxing bromobenzene they form halogenated penicillin analogs. (--)-Methyl 6-epi-6-bromobisnorpenicillinate (3a) and methyl 6-epi-6-bromopenicillinates (6a,b) have been prepared and isolated.     

Vibrational and electronic absorption spectra of 4-chloro 2-methyl, 4-chloro 3-methyl and 6-chloro 3-methyl phenols

The infrared spectra of 4-Cl 2-Me, 4-Cl 3-Me and 6-Cl 3-Me phenols have been recorded. The vibrational spectrum has been analysed assuming that the molecules belong toC _s point group and a tentative assignment of the observed frequencies to various modes of vibration has been proposed. The near ultraviolet absorption spectrum of these compounds has also been recorded. Assuming the transition to be electronically allowed the strongest band on the longer wavelength side has been assigned as the (0, 0) band in each case. The spectrum has been analysed in terms of several excited state frequencies which have been correlated with the ground state frequencies observed in the infrared spectrum.     

Ent-16β-羟基-16α-甲基贝叶烷的合成

四环二萜化合物在煤、原油、沉积物等地质样品中广泛存在，它是非常特征的陆源有机质输入生物标志物，以异斯特维醇为原料合成了Ｅｎｔ－１６β－羟基－１６α－甲基贝叶烷。产率达２１％。     

Efficient and fast Heck vinylation of 2-bromo-6-methyl pyridines with methylacrylate. Application to the synthesis of 6-methyl cyclopenta[b]pyridinone

Heck vinylation of 2-bromo-6-methyl-3-substituted pyridines using η³-allylpalladium chloride dimer/P(o-Tol)₃ complex/toluene and dimethylacetamide (DMA) as co-solvent with methyl acrylate is reported. Electronic and steric effects were investigated engaging diversely 2-bromo-3,6-disubstituted pyridines. As application, a new synthesis of the 6-methyl cyclopenta[b]pyridinone building-block connecting Heck vinylation, alkene reduction and Dieckmann condensation is described.     

A novel approach to the synthesis of 8-methyl prostaglandins

A synthesis of 8-methyl prostaglandins is described. Starting from a chiral cyclic keto lactone, C₁-homologation with dimethyl oxosulfonium methylide is used as key reaction in the sequence. 8-Methyl prostaglandin C₂ and its methyl ester proved to be quite unstable due to double-bond migration and dehydration.     

Condensations of dehydroacetic acid at the 6-methyl position

Dehydroacetic acid in the presence of two equivalents of sodium amide in liquid ammonia underwent methylation at the acetyl methyl position. In contrast, treatment of dehydroacetic acid with three equivalents of sodium amide converted it to a trianion which underwent condensations with electrophiles predominantly at the 6-Me position. The condensations included alkylation with alkyl halides, carbonyl addition with benzophenone, conjugate addition with chalcone, and acylation with aromatic esters. The benzoylation product was converted by acid treatment into 3,4-dihydroxy-6-methylbenzophenone. Methylation of both the 6-methyl and the acetyl methyl positions was accomplished by treatment of dehydroacetic acid trianion with excess methyl iodide.     

Separation and spectroscopic characterization of new metal chelates of 8-arylazo-6-formyl-7-hydroxy-5-methoxy-2-methyl chromones

Transition metal chelates of the title compounds have been prepared and characterized by elemental analyses, i.r., 1H-n.m.r., electronic spectra, thermogravimetric analysis, conductometric and magnetic measurements. Chelates of general formulae MLjX · nH2O for 1:1 (M:L), where X=OH– or Cl–, j=1 or 2, n=1– 4 and M=VO2+, Cr3+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+ ions or ML2 for 1:2 (M:L) Ni-(1a), ML2·2H2O where M=Co2+, Ni2+ and Cu2+ or M2LjX·nH2O for 2:1 (M:L) Cr3+, Fe2+, Ni2+ and Cu2+, L=Ligand, have been prepared. I.r. and 1H-n.m.r. spectra indicate that the aldehydic group in position six and the hydroxylic group in position seven are involved in chelation in the 1:1 and 1:2 (M:L) chelates, whereas for 2:1 (M:L) chelates with (1c), the interaction of the metal ion takes place through CHO, OH, CO2H and NN groups. Tetrahedral, octahedral and square planar geometries are proposed for the chelates based on their electronic spectra and magnetic moments.     

蛋氨酸合酶催化反应研究Ⅵ.3-N-取代-6-甲基尿嘧啶的合成

首次报道了以苄氧羰氧次甲基作为6-甲基尿嘧啶环上N1位的保护基.选择性的在尿嘧啶环上N1保护、N3取代及N1脱保护等反应都在简便、高收率条件下进行,经四步反应高选择性地合成了3-N-取代-6-甲基尿嘧啶.     

Contributions of the 8-methyl group to the vibrational normal modes of flavin mononucleotide and its 5-methyl semiquinone radical

Resonance Raman spectroscopy is a powerful tool to investigate flavins and flavoproteins, and a good understanding of the flavin vibrational normal modes is essential for the interpretation of the Raman spectra. Isotopic labeling is the most effective tool for the assignment of vibrational normal modes, but such studies have been limited to labeling of rings II and III of the flavin isoalloxazine ring. In this paper, we report the resonance and pre-resonance Raman spectra of flavin mononucleotide (FMN) and its N5-methyl neutral radical semiquinone (5-CH 3FMN(*)), of which the 8-methyl group of ring I has been deuterated. The experiments indicate that the Raman bands in the low-frequency region are the most sensitive to 8-methyl deuteration. Density functional theory (DFT) calculations have been performed on lumiflavin to predict the isotope shifts, which are used to assign the calculated normal modes to the Raman bands of FMN. A first assignment of the low-frequency Raman bands on the basis of isotope shifts is proposed. Partial deuteration of the 8-methyl group reveals that the changes in the Raman spectra do not always occur gradually. These observations are reproduced by the DFT calculations, which provide detailed insight into the underlying modifications of the normal modes that are responsible for the changes in the Raman spectra. Two types of isotopic shift patterns are observed: either the frequency of the normal mode but not its composition changes or the composition of the normal mode changes, which then appears at a new frequency. The DFT calculations also reveal that the effect of H/D-exchange in the 8-methyl group on the composition of the vibrational normal modes is affected by the position of the exchanged hydrogen, i.e., whether it is in or out of the isoalloxazine plane.     

Infrared and Raman spectra of vicinally trisubstituted 2-methyl, 3-chloroaniline and 2-methyl, 6-chloroaniline

The IR and Raman spectra of 2-methyl, 3-chloroaniline (2-M, 3-CA) and 2-methyl, 6-chloroaniline (2-M, 6-CA) have been recorded at room temperature in the region 3600-100 cm⁻¹. A vibrational analysis has been made using additional frequencies obtained from IR studies at 223 and 123 K and also including the polarization measurement of the Raman lines. A comparative study of these two molecules together with the spectra of 2,3-dimethylaniline (2,3-DMA), investigated earlier, has been presented. The anomalous behaviour of certain normal modes at low temperatures indicates the presence of an intermolecular hydrogen bonding of the N-H…N type in 2-M, 3-CA and 2,3-DMA, whereas, in 2-M, 6-CA, an intramolecular hydrogen bonding of the type N-H…Cl has been detected owing to the presence of the highly electronegative Cl atom at the ortho position.     

蛋氨酸合酶催化反应研究VI.3-N-取代-6-甲基尿嘧啶的合成

首次报道了以苄氧羰氧次甲基作为6-甲基尿嘧啶环上N1位的保护基．选择性的在尿嘧啶环上N1保护、N3取代及N1脱保护等反应都在简便、高收率条件下进行，经四步反应高选择性地合成了3-N-取代-6-甲基尿嘧啶。     

The N6-methyl group of adenine further increases the BI stability of DNA compared to C5-methyl groups

Methylated DNA bases are natural modifications which play an important role in protein-DNA interactions. Recent experimental and theoretical results have shown an influence of the base modification on the conformational behavior of the DNA backbone. MD simulations of four different B-DNA dodecamers (d(GC)(6), d(AT)(6), d(G(5mCG)(5)C), and d(A(T6mA)(5)T)) have been performed with the aim to examine the influence of methyl groups on the B-DNA backbone behavior. An additional control simulation of d(AU)(6) has also been performed to examine the further influence of the C5-methyl group in thymine. Methyl groups in the major groove (as in C5-methylcytosine, thymine, or N6-methyladenine) decrease the BII substate population of RpY steps. Due to methylation a clearer distinction of the BI substate stability between YpR and RpY (CpG/GpC or TpA/ApT) steps arises. A positive correlation between the BII substate population and base stacking distances is seen only for poly(GC). A methyl group added into the major groove increases mean water residence times around the purine N7 atom, which may stabilize the BI substate by improving the hydration network between the DNA backbone and the major groove. The N6-methyl group also forms a water molecule bridge between the N6 and O4 atoms, and thus further stabilizes the BI substate.     

Synthesis of 5-bromo-6-methyl imidazopyrazine, 5-bromo and 5-chloro-6-methyl imidazopyridine using electron density surface maps to guide synthetic strategy

Small heteroaromatic rings are valuable monomers in drug discovery that can enable rapid access to novel and desirable chemical space. Installation of a synthetic handle on a heteroaromatic core may be difficult if steric and electronic factors are not in alignment with the desired transformation. Described are practical routes for the construction of 5-bromo-6-methyl imidazopyrazine (1) as well as 5-bromo and 5-chloro-6-methyl imidazopyridines (2a and 2b), which were developed using electron density surface maps encoded with ionization potential to guide synthetic strategy.