Use of pi-allyltricarbonyliron lactone complexes in the synthesis of taurospongin A: a potent inhibitor of DNA polymerase beta and HIV revers transcriptase

The total synthesis of taurospongin A by two new approaches has been achieved where pi-allyltricarbonyliron lactone complexes have been used to control highly stereoselective additions of the nucleophiles to a carbonyl unit located in the side chain of these complexes.     

Primary amido substituted diborane4 compounds and imidodiborate4 anions

Treatment of the diborane(4) compound B(2)(NMe(2))(4) with aniline or 2,6-dimethylaniline results in the primary amido compounds B(2)(NHR)(4)(R = Ph, 2,6-Me(2)C(6)H(3)); subsequent treatment with n-BuLi in toluene in each case affords the first examples of anionic imidodiborates namely Li(4)(thf)(6)B(2)(NPh)(4) and Li(4)(thf)(4)B(2)(N-2,6-Me(2)C(6)H(3))(4); all complexes have been characterised crystallographically.     

Determination of ammonia based on the electro-oxidation of hydroquinone in dimethylformamide or in the room temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide

The results detail a novel methodology for the electrochemical determination of ammonia based on its interaction with hydroquinone in DMF. It has been shown that ammonia reversibly removes protons from the hydroquinone molecules, thus facilitating the oxidative process with the emergence of a new wave at less positive potentials. The analytical utility of the proposed methodology has been examined with a linear range from 10 to 95 ppm and corresponding limit-of-detection of 4.2 ppm achievable. Finally, the response of hydroquinone in the presence of ammonia has been examined in the room temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluormethylsulfonyl)imide, [EMIM][N(Tf)₂]. Analogous voltammetric waveshapes to that observed in DMF were obtained, thereby confirming the viability of the method in either DMF or [EMIM][N(Tf)₂] as solvent.     

Synthesis and solid-state structures of new cyclophane host molecules

Five new cyclophane host molecules (corrals) are prepared by linking together two α,α′-di(4-hydroxyphenyl)-1,4-diisopropylbenzene or α,α′-di(3,5-dimethyl-4-hydroxyphenyl)-1,4-diisopropylbenzene units with two permethylene spacers. Three small cyclophane hosts (boxes) are synthesized by cyclization of α,α′-di(4-hydroxyphenyl)-1,4-diisopropylbenzene with di(bromomethyl)benzene compounds. Solid-state structures of one corral and one box are reported.     

An Asymmetric Synthesis of L-694,458, a Human Leukocyte Elastase Inhibitor, via Novel Enzyme Resolution of beta-Lactam Esters

A convergent synthesis of [S-(R,S)]-2-[4-[(4-methylpiperazin-1-yl)carbonyl]phenoxy]-3,3-diethyl-N-[1-[3,4-(methylenedioxy)phenyl]butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates: (S)-3,3-diethyl-4-[4'-[(N-methylpiperazin-1-yl)carbonylphenoxy]-2-azetidinone (2) and (R)-alpha-propylpiperonyl isocyanate (3). Synthesis of beta-lactam 2 was achieved by a novel enantioselective lipase hydrolysis of ester 5 to produce (S)-3,3-diethyl-4-(4'-carboxyphenoxy)-2-azetidinone (6) (60% yield, three cycles, 93% ee) with isolation, epimerization, and recycling of the undesired (R)-ester 5. Isocyanate 3 was prepared by chiral addition of Zn(n-Pr)(2) to piperonal (98% yield, 99.2% ee), azide displacement and reduction to (R)-alpha-propylpiperonylamine (11) (58% yield, 85% ee), crystallization as the D-pyroglutamic acid salt (92% yield, 98.2% ee), and isocyanate formation (98% yield) with phosgene.     

Detection and assessment of citrus tristeza virus antigens by computer-aided scanning densitometry

Citrus tristeza virus (CTV) extracted from Etrog citron (C.medica L.) was immunoprecipitated. The immunoprecipitate was fractionated by SDS-PAGE and western blotted onto nitrocellulose. The CTV antigens were determined by immunoblot analysis using rabbit anti-CTV IgG, and the protein-band pattern exhibited on the nitrocellulose was assessed by soft-laser scanning densitometry. The densitometric tracing revealed the presence of bands that were not visible to the naked eye. Using the superimposition mode of the instrument, it was also revealed that the protein-band patterns of different CTV samples were not identical. Computer-aided soft-laser scanning densitometry proved to be a powerful approach in the detection and assessment of protein bands revealed on nitrocellulose immunoblots, which we were previously unable to do employing conventional methods.     

Tandem GC/MS: A useful tool for studying end-capping reactions of oligo(styryl)lithium anions

Anionic living polymerization methods, using organometallic initiators such as butyllithium reagents, have proven useful for, inter alia, styrene polymerization and are amenable to subsequent functionalization of poly(styryl)lithium in the termination step. In this study, general methods for the selective preparation of small styrene oligomers and termination of the intermediate oligo(styryl)lithium anions were investigated. The crude reaction mixtures were analyzed directly by tandem gas chromatography/mass spectrometry (GC/MS). Of the carbon- and silicon-based electrophiles tested, chloro(chloroalkyl)silanes, Cl-SiR₂(CH₂)_nCl in particular, were shown by GC/MS to be regioselective end-capping reagents, thus allowing subsequent transformation to the primary amine. The combined GC/MS data allow not only an estimate of the degree of functionalization, but also the identification of by-products, thus providing insight into the end-capping process that otherwise might be difficult to access. © 1995 John Wiley & Sons, Inc.     

Effects of alkali metal halide salts on the hydrogen bond network of liquid water

Measurements of the oxygen K-edge X-ray absorption spectrum (XAS) of aqueous sodium halide solutions demonstrate that ions significantly perturb the electronic structure of adjacent water molecules. The addition of halide salts to water engenders an increase in the preedge intensity and a decrease in the postedge intensity of the XAS, analogous to those observed when increasing the temperature of pure water. The main-edge feature exhibits unique behavior and becomes more intense when salt is added. Density functional theory calculations of the XAS indicate that the observed red shift of the water transitions as a function of salt concentration arises from a strong, direct perturbation of the unoccupied molecular orbitals on water by anions, and does not require significant distortion of the hydrogen bond network beyond the first solvation shell. This contrasts the temperature-dependent spectral variations, which result primarily from intensity changes of specific transitions due to geometric rearrangement of the hydrogen bond network.     

Cooperativity, partially bound states, and enthalpy-entropy compensation

Efforts to develop a quantitative understanding of molecular recognition rely on the additivity of individual intermolecular interactions, and cooperativity represents one of the major potential stumbling blocks. A chemical double-mutant cycle has been used to experimentally measure cooperativity between functional group interactions within a complex framework. The interaction between two aromatic groups varies by 0.2 +/- 0.4 kJ mol(-1) in synthetic H-bonded complexes that differ by 8-13 kJ mol(-1) in overall stability. In these systems, the free energies associated with individual intermolecular interactions can therefore be reliably treated in an additive fashion. The results suggest that alternative explanations should be considered for cooperative phenomena observed in other systems, and a rationale based on the population of partially bound states in flexible molecules is proposed to account for the enthalpic chelate effect and enthalpy-entropy compensation.     

Synthesis of (+)-2R,3R,11R,12R- and (−)-2S,3S,11S,12S-tetraphenyl-18-crown-6

The synthesis of the title crown ethers starting from optically active hydrobenzoins is described. R(+)-1,in CDCl₃ ,preferentially extracts R(+)-phenylglycine methyl ester hydroperchlorate from an aqueous solution of the racemate with a chiral recognition factor of 1.5 as shown by nmr measurements.