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Six novel unsymmetrical diglycolamide (UDGA) ligands have been synthesized and evaluated as solvent extraction reagents for the partitioning of lanthanide (Ln) ions from nitrate media. The partitioning of europium between aqueous phases of varying nitric acid concentrations and a UDGA organic phase has been characterized radiometrically. The stoichiometry and phase-transfer equilibrium constants of the Eu-UDGA complexes extracted into the organic phase have been reported. Luminescence spectroscopy investigations have established the relative stability and stoichiometry of the complexes in acetonitrile. These UDGA ligands have displayed enhanced interfacial activity, which has decreased the necessary equilibration time while maintaining high Ln distribution ratios.

A new preparative route to Oppolzer's glycylsultam, the 'NC' component in the asymmetric [C+NC+CC] coupling reaction leading to functionalized pyrrolidines, is described. The synthesis features a novel application of the Delepine reaction, providing a safe, efficient, and environmentally benign route to this useful chiral reagent for pyrrolidine synthesis.

Thio-ether bonds in the cysteinyl side-chain of peptides, formed with the most commonly used cysteine blocking reagent iodoacetamide, after conversion to sulfoxide, releases a neutral fragment mass in a low energy MS/MS experiment in the gas-phase of the mass spectrometer [Steen et al. J Am Soc Mass Spectrom. 2001, 12, 228–32.]. In this study, we show that the neutral loss fragments produced from the mono-oxidized thio-ether bonds (sulfoxide) in peptides, formed by alkyl halide or double-bond containing cysteine blocking reagents are different under low energy MS/MS conditions. We have evaluated the low energy fragmentation patterns of mono-oxidized modified peptides with different cysteine blocking reagents, such as iodoacetamide, 3-maleimidopropionic acid, and 4-vinylpyridine using FTICR-MS. We propose that the mechanisms of gas-phase fragmentation of mono-oxidized thio-ether bonds in the side-chain of peptides, formed by iodoacetamide and double-bond containing cysteine blocking reagents, maleimide and vinylpyridine, are different due to the availability of acidic β-hydrogens in these compounds. Moreover, we also investigated the fragmentation characteristics of mono-oxidized thio-ether bonds within the peptide sequence in order to develop novel mass-spectrometry identifiable chemical cross-linkers. This methionine type of oxidized thio-ether bond within the peptide sequence did not show anticipated low energy fragmentation. Electron capture dissociation (ECD) of the side-chain thio-ether-bond containing oxidized peptides was also studied. ECD spectra of the oxidized peptides showed a greater extent of peptide backbone cleavage, as compared to CID spectra. This fragmentation information is critical to researchers for accurate data analysis of this undesired modification in proteomics research, as well as other methods that may utilize sulfoxide derivatives.

This work reports the separation of FTC enantiomers using an amylose tris[( S )-1-phenylethylcarbamate] coated onto APS-Nucleosil (7 μm particle size, 500 A pore size, 20% w/w, 15×0.46 cm ID) chiral column under polar organic elution mode. Good enantioselectivity ( α =1.9) with excellent enantioresolution ( R S =3.3) was achieved by the use of methanol with 0.02% of triethylamine acetate as mobile phase. The method allows the accurate determination of as low as 0.2% of each enantiomer as an impurity. The validated method proved to be reliable and sensitive for the quantification of both enantiomers as impurity in different batches of emtricitabine and β- d -(+)-FTC.

We report a three-step synthesis of (R)-propylene carbonate from inexpensive, chiral ethyl (S)-lactate. The synthesis involves a borohydride ester reduction and an unusual intramolecular displacement reaction by a carbonate anion. The procedure is simple and reliable, resulting in (R)-propylene carbonate in approximately 60% overall yield with ≥98% ee.

The methoxymethoxy substituent when attached to an aromatic ring functions as a moderately strong ortho-directing group in hydrogen-metal exchange reactions. In many cases the propensity of the methoxymethoxylated arene toward ring metallation is greatly enhanced with concomitant suppression of undesirable side reactions such as nucleophilic attack and addition of the metallating species. Unlike many other ortho-directing groups, the regio-direction of the methoxymethoxy substituent when in conjunction with other weaker directing groups is dependent upon the metalating medium. Thus, by changing the electron donating capacity of the metallating medium it is possible to selectively direct metallation to either of the positions ortho to the methoxymethoxy substituent.

By means of spectral and chemical studies the structure of Grahamimycin A1 1 , a novel macrocyclic dilactone antibiotic from Cytospora, is established.

Synthese a partir de l'acide t-butyldiphenylsiloxy-7 octyne-4oique et de l'hydroxy-5 hexene-2oate de benzhydryle

Recently, during studies directed toward the total synthesis of the antibiotic frustulosin 11,2 we encountered some problems in the removal of methoxyl groups during the preparation of the phenolic aldehyde 2. Our efforts to effect this transformation led us to investigate the reactions of the boron trihalides with aromatic aldehydes. Although the methoxyl group has many desirable properties for hydroxyl protection its stability to both acids and bases often presents difficulties at the time of removal. Of the many reagents and methods devised3 for the removal of methoxyl and other alkoxyl groups boron tribromide can be considered as one of the most widely applicable reagents for this purpose. However, as a fairly powerful Lewis acid, complications can arise when acid.

Stereoselective rearrangement of cis-5-(4-methoxybenzyl)-spiro[5,2]-octan-4-ol cis-1 in acidified THF-90% H 2 O 2 affords 9-oxabicyclo[6.2.1]nonyl hydroperoxides 7 and 8 which are converted to medium-ring, keto-butyrolactones 2 and 3.

Ketones are readily spiroannelated by 2-chloroethyldimethyl sulfonium iodide 1 in the presence of t-butoxide anion in t-butanol. The procedure affords a simple one step -spirocyclopropanation of ketones in good yields.

Rearrangement of spiro[5,2]octan-4-ol, 1, in acidified THF-H2O2 is a selective process in which substitution occurs with retention of configuration and ring-expansion with inversion of the carbinyl center.

Synthese de la broussonine A (methoxy-4 trimethylene-2,4' bis-phenol) a partir de l'hydroxy-4 benzenepropanol

The revised structure of the novel antibiotic frustulosin is confirmed by regioselective total synthesis.

(+)-(1 S )-Fenchone, an irregular bicyclic monoterpene ketone thought to be derived via rearrangement of a bicyclic precursor, is one of the major terpenoids of the volatile oil of fennel ( Foeniculum vulgare M.). A soluble enzyme preparation obtained from homogenates of young fennel leaves converted the acyclic precursors geranyl pyrophosphate and neryl pyrophosphate to fenchol in the presence of Mn 2+ , and in the presence of pyridine nucleotide, dehydrogenated the fenchol formed to fenchone. Particulate enzyme fractions were inactive in the synthesis of fenchane-type monoterpenes. The identities of the biosynthetic products as fenchol and fenchone were confirmed by radiochromatographic analysis and by the synthesis of crystalline derivatives. Differential crystallization of the fenchyl hydrogen phthalates and the fenchyl p -nitrobenzoates demonstrated that the initial cyclic product was endo -[ 3 H]fenchol and not the exo -epimer, while resolution of [ 3 H]fenchone oxime via the diastereomeric l -menthyloxymethyl ethers confirmed the stereochemistry of the labeled cyclic products as (−)-(1 S )- endo -fenchol and (+)-(1 S )-fenchone. Biosynthetic l-endo -[ 3 H]fenchol derived from the [1- 3 H]-labeled acyclic precursors was chemically converted to (+)-(1 R )-α-fenchocamphorone, and exchange of the α-protons of this derivative established that 3 H was located specifically on the bridge carbon (C-7) of the original fenchane nucleus. Thus, the bicyclic fenchane skeleton was shown to be derived by rearrangement of a pinane-type intermediate. These results provide strong evidence that fenchone is derived by the cyclization of geranyl pyrophosphate or neryl pyrophosphate to endo -fenchol followed by dehydrogenation of this bicyclic alcohol, and they constitute the first demonstration of the biosynthesis of a rearranged monoterpene in a cell-free system.

Publisher Summary The terpenes constitute one of the largest and most structurally varied groups of natural products, and they exhibit a tremendous diversity in chromatographic properties, both within and between the various classes. This chapter focuses on the chromatography of relevant higher and lower isoprenalogs. The terpenoid vitamins (A, E, and K) have each been dealt with separately. Phosphorylated terpenes and glycosylated terpenes are described as these derivatives exhibit profound chromatographic differences relative to their parent terpenyl moieties. The chromatographic isolation of mevalonic acid (or mevalonolactone) is often required in the preparation of this isotopically labeled substrate for studies on isoprenoid biosynthesis, and, in the assay of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase), a key regulatory enzyme of the isoprenoid pathway. The enzyme assay generally involves the separation of the product, mevalonic acid (as the derived lactone), from the substrate, HMG CoA (often determined as HMG). Several simple thin layer chromatography (TLC) methods have been devised for this purpose, including chromatography on silica gel with acetone-benzene (1:1) and other developing solvents, or on Super-Cel–CaSO 4 (3:1) or cellulose.

A soluble enzyme preparation from the leaves of fennel (Foeniculum vulgare M.) has been shown to catalyze the cation-dependent cyclization of both geranyl pyrophosphate and neryl pyrophosphate to the bicyclic rearranged monoterpene l-endo-fenchol (R. Croteau, M. Felton, and R. Ronald, 1980 Arch. Biochem. Biophys.200, 524–533) . To examine the possible presence of free intermediates between the acyclic precursors and fenchol, and to remove competing cyclase and pyrophosphatase activities, the soluble preparation was partially purified by ammonium sulfate fractionation followed by gel filtration on Sephadex G-150 and ion exchange chromatography on O-diethylaminoethyl-cellulose. Activities for the cyclization of geranyl pyrophosphate and neryl pyrophosphate to fenchol were coincident on Chromatographic fractionation suggesting that the same enzyme was capable of cyclizing both acyclic substrates. No interconversion of the acyclic precursors was detected. Although bornyl pyrophosphate is a free intermediate in the biosynthesis of the related bicyclic monoterpenol borneol, both protein fractionation and isotopic dilution experiments ruled out endo-fenchyl pyrophosphate as a free intermediate in fenchol biosynthesis. Similarly, while construction of the fenchane skeleton was demonstrated to involve the rearrangement of an intermediate pinane skeleton, isotopic dilution experiments ruled out both optical antipodes of α-pinene, β-pinene, cis-2-pinanol, trans-2-pinanol, and the corresponding 2-pinyl pyrophosphates as free intermediates of the enzyme-catalyzed reaction. Furthermore, exhaustive search of the enzymatic reaction products provided no evidence to suggest the involvement of any free intermediate between the acyclic precursor and fenchol. The endo-fenchol synthetase has an apparent molecular weight of 60,000, shows a pH optimum near 7.0, and requires Mn2+ (1 m m ) for catalytic activity. Co2+ can partially substitute for Mn2+, but other divalent cations are ineffective. The partially purified synthetase is inhibited by p-hydroxymercuribenzoate and by phenylglyoxal, and it exhibits a preference for geranyl pyrophosphate over neryl pyrophosphate as substrate. An integrated scheme is proposed for the cyclization and rearrangement catalyzed by fenchol synthetase.

The revised structure of the novel antibiotic frustulosin is confirmed by regioselective total synthesis.

A method for the determination of organolithium reagent is described using 2,5-dimethoxybenzyl alcohol as a self-indicating primary standard.