Highly diastereoselective chemoenzymatic synthesis of (2′R)- and (2′S)-2′-deoxy[2′-H]guanosines

In an effort to develop an efficient synthetic method of highly diastereoselective (2′R)- and (2′S)-2′-deoxy[2′-²H]guanosines, chemoenzymatic conversion was investigated. The synthesis of (2′R > 98% de)-2′-deoxy[2′-²H]guanosine was achieved by biological transdeoxyribosylation using (2′R > 98% de)-2′-deoxy[2′-²H]uridine, 2,6-diaminopurine, and Enterobacter aerogenes AJ-11125, followed by treatment with adenosine deaminase. (2′S > 98% de)-2′-Deoxy[2′-²H]guanosine was synthesized from (2′S > 98% de)-2′-deoxy[2′-²H]uridine and 2,6-diaminopurine using thymidine phosphorylase and purine nucleoside phosphorylase instead of E. aerogenes AJ-11125.     

A single chalcone and additional rotenoids from Lonchocarpus nicou

The lipophile extract of Lonchocarpusnicou roots afforded the new pyranochalcone 3-O-methylabyssinone A as well as the new rotenoids 7′-hydroxytephrosin, and 7′-nor-6′-oxo-2′,3′-dehydrorotenone, both compounds occurring with the known 7′-hydroxydeguelin and 7′-nor-6′-oxo-2′,3′-dehydro-12aβ-hydroxyrotenone. Furthermore, two rotenoid epoxides previously reported as resulting from the direct oxidative conversion of rotenone and 12aβ-hydroxyrotenone, respectively, were isolated for the first time from a plant source. All the structures were established on the basis of UV, MS, and NMR data.     

Characterization of Ascentis RP-Amide column: Lipophilicity measurement and linear solvation energy relationships

This study investigates lipophilicity determination by chromatographic measurements using the polar embedded Ascentis RP-Amide stationary phase. As a new generation of amide-functionalized silica stationary phase, the Ascentis RP-Amide column is evaluated as a possible substitution to the n  -octanol/water partitioning system for lipophilicity measurements. For this evaluation, extrapolated retention factors, log k^′_w$\text{log}{k^{\prime }}_w$, of a set of diverse compounds were determined using different methanol contents in the mobile phase. The use of n-octanol enriched mobile phase enhances the relationship between the slope (S  ) of the extrapolation lines and the extrapolated log k^′_w$\text{log}{k^{\prime }}_w$ (the intercept of the extrapolation), as well as the correlation between log P   values and the extrapolated log k^′_w$\text{log}{k^{\prime }}_w$ (1:1 correlation, r² = 0.966). In addition, the use of isocratic retention factors, at 40% methanol in the mobile phase, provides a rapid tool for lipophilicity determination. The intermolecular interactions that contribute to the retention process in the Ascentis RP-Amide phase are characterized using the solvation parameter model of Abraham. The LSER system constants for the column are very similar to the LSER constants of the n-octanol/water extraction system. Tanaka radar plots are used for quick visual comparison of the system constants of the Ascentis RP-Amide column and the n-octanol/water extraction system. The results all indicate that the Ascentis RP-Amide stationary phase can provide reliable lipophilic data.     

A simple and stereodivergent strategy for the synthesis of 3′-C-branched 2′,3′-dideoxynucleosides exploiting (Z)-but-2-en-1,4-diol and (R)-2,3-cyclohexylideneglyceraldehyde

Barbier type additions of allylic bromide 4, derived from (Z)-but-2-en-1,4-diol 2 to (R)-2,3-cyclohexylideneglyceraldehyde 1 were performed through mediation with Zn employing Luche’s procedure and also with low valent Cu, Co, and Fe which were produced via bimetal redox strategy in THF to afford 5c,d as the major products. From these, 5a,b were prepared following an oxidation-reduction protocol. Compound 5c was exploited as a representative starting material to develop a simple and inexpensive strategy toward the synthesis of 3′-C-branched 2′,3′-dideoxynucleosides having stereodiversity at 3′- and 4′-positions.     

Improved synthesis of N-alkyl substituted dithieno[3,2-b:2′,3′-d]pyrroles

A new, convergent and improved synthetic method to prepare N-alkyl substituted dithienopyrroles is described. The procedure consists of a Pd-catalyzed amination of 3,3′-dibromo-2,2′-bithiophene. The reaction conditions were optimized, which makes this method applicable to prepare these molecules easily in high yields and on a large scale.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

A new equation to reproduce the enthalpies of transfer of formamide, N-methylformamide and N,N-dimethylformamide from water to aqueous methanol mixtures at 298 K

The enthalpies of transfer of formamide (Form) N-methylformamide (NMF) and N,N-dimethylformamide (DMF) from water to aqueous methanol mixtures are reported and analysed in terms of the new solvation theory. It was found that a previous equation could not reproduce these data over the whole range of solvent compositions. Using the new solvation theory to reproduce the enthalpies of transfer shows excellent agreement between the experimental and calculated data over the entire range of solvent compositions. The analyses show that the solvation of DMF is random in the aqueous methanol mixtures while Form and NMF are preferentially solvated by methanol. It is also found that the interaction of the solutes is stronger with methanol than with water.     

Acid-catalyzed condensation of 2,2′-diamino-1,1′-biaryls for the synthesis of benzo[c]carbazoles

2,2′-Diamino-1,1′-biaryls were found to undergo ring-closure condensation reaction to afford benzo[c]carbazoles in good to excellent yield. Coupled with the synthesis of 2,2′-biaryldiamines from diaryl hydrazides via [3,3]-sigmatropic rearrangement, it constitutes a new efficient synthetic method for benzo[c]carbazoles and related compounds.     

N,N′,N″-Tri-Boc-guanidine (TBG): a common starting material for both N-alkyl guanidines and amidinoureas

In this Letter, we describe the unexpected reaction pattern of N,N′N″-tri-Boc-guanidine (TBG) with amines at room temperature and under reflux conditions affording N-substituted guanidines and amidinoureas, potentially important compounds with extensive applications in medicinal chemistry. This investigation shows that TBG is an excellent, readily available common starting material for the synthesis of various N-alkyl guanidines as well as N-alkyl-N′-substituted amidinoureas by simply manipulating the reaction conditions.     

Selective palladium-catalyzed amination of the heterocyclic core of variolins

A new and selective palladium-catalyzed amination of the pyrido[3′,3′:4,5]pyrrolo[1,2-c]pyrimidine nucleus, the heterocyclic core of the variolin alkaloids, is described. The method allows the introduction of amino and aryl- and alkylamino substituents on the C9 position in advanced precursors of variolin B and deoxyvariolin.     

DFT study of the reaction sites of N,N′-substituted p-phenylenediamine antioxidants

The geometry of N,N′-diphenyl-p-phenylenediamine (DPPD), N-phenyl-N′-(1′-methylbenzyl)-p-phenylenediamine (SPPD), N-phenyl-N′-(1,3-dimethyl-butyl)-p-phenylenediamine (6PPD), N-phenyl-N′-isopropyl-p-phenylenediamine (IPPD), and N-(1-methyl-1-phenylethyl)-N′-phenyl-p-phenylenediamine (CPPD) as well as of their dehydrogenation products has been optimized at B3LYP/6-31G^∗ level of theory. Our results support the idea of formation of stable ketimine Ph-NC structures (instead of quinonediimine structures) during consecutive dehydrogenation of SPPD, 6PPD, and IPPD antioxidants despite the formation of tertiary carbon-centered radicals in the first dehydrogenation step is energetically preferred for SPPD only.     

A novel one-pot and efficient procedure for the synthesis of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones

A novel and practical one-pot procedure is described for the preparation of several new of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones based on the addition reaction of ninhydrin and 6-aminouracils followed by oxidative cleavage of their corresponding dihydroxyindenopyrrolopyrimidines.     

A concise synthesis of asymmetrical N,N′-disubstituted guanidines

We present a new and concise method for the preparation of asymmetrical N,N′-disubstituted guanidines starting from thiourea via the reaction of N-Boc-protected N′-alkyl/aryl substituted thioureas with an amine in the presence of mercury(II) chloride and triethylamine.     

N,N,N,N-Tetramethyl-1,3-propanediamine as the catalyst of choice for the Baylis-Hillman reaction of cycloalkenone: rate acceleration by stabilizing the zwitterionic intermediate via the ion-dipole interaction

N,N,N^′,N^′-Tetramethyl-1,3-propanediamine (TMPDA) can be used as an efficient catalyst for the Baylis-Hillman reaction of cycloalkenones. The increased reaction rate was thought be derived from the stabilizing effect of the zwitterionic intermediate via the ion-dipole interaction.     

An efficient synthesis of new 1-H-4′-methyl-3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinoline] scaffolds

Efficient synthesis of new 3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinolines] by a four step synthetic route based on 1-benzyl-4-piperidone reactivity is reported.     

Flow-injection spectrophotometry of vanadium by catalysis of the bromate oxidation of N,N'-bis(2-hydroxyl-3-sulfopropyl)-tolidine

A highly sensitive flow-injection method is proposed for the catalytic determination of vanadium(V) at sub-nanogram per milliliter levels using a new indicator reaction. The method is based on the catalytic effect of vanadium(V) on the bromate oxidation of N,N′-bis(2-hydroxyl-3-sulfopropyl)-tolidine. 1,2-Dihydroxybenzene-3,5-disulfonate was used as an activator in the vanadium(V)-catalyzed reaction and significantly enhanced the sensitivity of the method. Vanadium(V) in the range 0.01-3.0 ng ml⁻¹ was easily determined with sampling rate of about 30 h⁻¹. Vanadium(IV) could be also determined. The limit of detection (S/N=3) was 0.008 ng ml⁻¹ and the relative standard deviations were 1.4 and 1.6% for ten determinations of 0.2 ng ml⁻¹ vanadium(IV) and vanadium(V), respectively. Interferences from metal ions could be suppressed by the addition of ethylenediamine-N,N,N′,N′-tetrakis(methylenephosphonic acid) as a masking agent. The proposed method was successfully applied to the determination of vanadium in water samples.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

Diarylnonanoids and their glucosides from Erica cinerea

The reinvestigation of Erica cinerea fresh aerial parts led to the isolation of two new diarylnonanoid aglycones along with their glucosides. From spectroscopic data, their structures were elucidated as rel-(3R,7R)-1,9-bis(p-hydroxyphenyl)-3,7-dihydroxynonan-5-one named ericanone, ericanone 3-β-d-glucoside, (3S)-3,7-anhydro-6,7-dehydroericanone and (3S)-3,7-anhydro-6,7-dehydroericanone 4′-β-d-glucoside. Contrary to the numerous diarylheptanoids more frequently distributed in the plant kingdom, the rare diarylnonanoids were previously restricted to the genus Myristica of the Myristicaceae plant family.     

Convenient synthesis of N-isobutyryl-2′-O-methyl guanosine by efficient alkylation of O-trimethylsilylethyl-3′,5′-di-tert-butylsilanediyl guanosine

We present a novel route for the synthesis of N²-isobutyryl-2′-O-methyl guanosine, introducing 3′,5′-di-tert-butylsilyl and O⁶-trimethylsilylethyl groups as efficient protections during the 2′-O-methylation step with NaH/CH₃I. These protections were then removed simultaneously in a single step with TBAF. The eight-step synthesis is easy to perform, employing convenient commercially available reagents; crude mixtures are of satisfying purity, so only three chromatography purifications were required. Title compound was obtained in 25% overall yield from guanosine.