Diastereoisomeric Pairs Research Articles

3 + 2] Cycloreversion of bicyclo[m.3.0]alkan-3-on-2-yl-1-oxonium ylides to alkenyloxyketenes. Stereospecific aspect.

Rhodium(II)-catalyzed intramolecular reaction of diazoketones 1 bearing a cyclic ethereal moiety transiently formed bicyclo[m.3.0]octan-3-one-1-oxonium-2-ylides (2), which underwent sigmatropic and stereospecific [3 + 2] cycloreversion reaction to form alkenyloxyketenes 3. The ketenes were efficiently trapped by methanol to form the corresponding esters 4. Mechanistic studies revealed that the size of ethereal ring can be variable at least from THF to the THP, oxepane, and oxocane moiety, i.e., m = 3-6. On the other hand, the size of the ylide ring containing the carbonyl unit is limited to a five-membered ring. The cycloreversion was found to be stereospecific as was proven by the reactions of diastereoisomeric pairs bearing a methyl group at the bond-cleaving position. From threo isomers 7, (E)-alkenyloxyacetates 15 were exclusively formed (77-84%), whereas from erythro isomers 8, (Z)-isomers 16 were formed (80-88%). Mechanism of the cleavage from diazoacetonyl-substituted cyclic ethers to alkenyloxyketenes via bicyclic oxonium ylides was analyzed on the basis of calculations employing the hybrid density functional B3LYP and the highly correlated quadratic configuration interaction QCISD method to reveal that the concerted [3 + 2] cycloreversion is the key step of this reaction.

Stereoselective excision of thymine glycol from oxidatively damaged DNA.

DNA damage created by reactive oxygen species includes the prototypic oxidized pyrimidine, thymine glycol (Tg), which exists in oxidatively damaged DNA as two diastereoisomeric pairs. In Escherichia coli, Saccharomyces cerevesiae and mice, Tg is preferentially excised by endonuclease III (Endo III) and endonuclease VIII (Endo VIII), yNTG1 and yNTG2, and mNTH and mNEIL1, respectively. We have explored the ability of these DNA glycosylases to discriminate between Tg stereoisomers. Oligonucleotides containing a single, chromatographically pure (5S,6R) or (5R,6S) stereoisomer of Tg were prepared by oxidation with osmium tetroxide. Steady-state kinetic analyses of the excision process revealed that Endo III, Endo VIII, yNTG1, mNTH and mNEIL1, but not yNTG2, excise Tg isomers from DNA in a stereoselective manner, as reflected in the parameter of catalytic efficiency (kcat/Km). When DNA glycosylases occur as complementary pairs, failure of one or both enzymes to excise their cognate Tg stereoisomer from oxidatively damaged DNA could have deleterious consequences for the cell.

Diastereotopic analysis of mesoridazine besylate (Serentil).

NMR studies were conducted with the aim of determining the diastereoisomeric ratio of a commercially supplied sample of mesoridazine (MES) and to compare the results with a freshly synthesised sample of MES. The results indicated that the commercially supplied MES consisted almost entirely of one diastereoisomeric pair, which was in agreement with previous findings reported by Eap et al. The synthesised sample of MES was analysed by NMR in two stages: 1) as the initial product isolated as the free base from the direct synthesis, and 2) as the free base isolated from the crystallised besylate salt of the synthetic product. The NMR results show that the initial synthetic product consisted of two equal pairs of diastereoisomers. The diastereoisomeric pairs were further separated by the addition of the chiral shift reagent (R)-(-)-N-(3,5 dinitrobenzoyl)-alpha-benzylamine to reveal equal quantities of all four enantiomers, clearly observed at the methyl sulfoxide proton peak of the NMR scan. The sample obtained from the crystallisation of MES besylate, however, indicated a significant difference, with a diastereoisomeric ratio of 75:25. The results suggest that MES besylate undergoes preferential crystallisation of one pair of diastereoisomers, with the other pair remaining in solution.

C2 symmetrical double chromophores: cooperativity effects in lanthanide ion complexation.

We describe the synthesis and characterization of C(2) symmetrical double chromophores, in which two identical chromophores are linked through ethylene glycol spacers of increasing lengths. The complexation ability of the trans stereopure form for each diastereoisomeric pair showed how the two chromophores, when the spacer unit is comprised of a diethylene or a triethylene glycol moiety, are able to interact in a positive way, stabilizing the resulting complexes when compared with single chromophore analogous compounds.

Barriers to internal rotation around the C-N bond in 3-(o-aryl)-5-methyl-rhodanines using NMR spectroscopy and computational studies. Electron density topological analysis of the transition states.

We have investigated the pairs of rotational isomers for six 3-(o-aryl)-5-methyl-rhodanines (Z = H, F, Cl, Br, OH, and CH3) using NMR spectroscopy and density functional theory (DFT) calculations. Electron density topological and NBO analysis has demonstrated the importance of non-covalent interactions, characterised by (3, -1) bond critical points (BCPs), between the oxygen and sulfur atoms on the thiazolidine ring with the aryl substitutents in stabilizing the transition states. The energetic activation barriers to rotation have also been determined using computational results; rotational barriers for 3-(o-chlorophenyl)-5-methyl-rhodanine (3S) and 3-(o-tolyl)-5-methyl-rhodanine (6S) were determined experimentally based on NMR separation of the diastereoisomeric pairs, and the first-order rate constants used to derive the value of the rotational barrier from the Eyring equation.

Characterization and quantification of metabolites of racemic ketoprofen excreted in urine following oral administration to man by 1H-NMR spectroscopy, directly coupled HPLC-MS and HPLC-NMR, and circular dichroism

The identity of the human metabolites of ketoprofen (2-(3-benzoylphenyl)-propanoic acid) excreted via urine was investigated after a single oral dose of the racemic drug.Drug metabolites were concentrated and partially purified from urine using solid-phase extraction chromatography before separation and identification by directly coupled HPLC-MS and HPLC-NMR.The metabolites identified were the ester glucuronides of the parent drug and its phase I metabolites, 2-[3-(3-hydroxybenzoyl)phenyl]-propanoic acid, 2-[3-(4-hydroxybenzoyl)phenyl]-propanoic acid and 2-[3-(hydroxy(phenyl)methyl)phenyl]-propanoic acid, the latter formed by reduction of the ketone group of ketoprofen. In addition, two novel minor metabolites were identified as the ether glucuronides of 2-[3-(3-hydroxybenzoyl)phenyl]-propanoic acid and 2-[3-(4-hydroxybenzoyl)phenyl]-propanoic acid. These conjugates were all observed as diastereoisomeric pairs of unequal proportions.Purification of these metabolites by preparative chromatography allowed stereochemistry assignments.Metabolites were quantified by 1H-NMR spectroscopy after spectral simplification achieved by hydrolysis of the conjugates.

Oligosaccharide-peptide ligation of glycosyl thiolates with dehydropeptides: synthesis of S-linked mucin-related glycopeptide conjugates.

A chemoselective strategy for oligosaccharide-peptide ligation is described in which alpha-thio analogues of mucin-related glycoconjugates can be readily accessed through site-selective conjugate addition of complex oligosaccharide thiolates to dehydroalanine-containing peptides. The efficiency of the ligation is highlighted by the rapid convergent assembly of thio-isosteres of the four tumor-associated carbohydrate antigens, T(N), T, ST(N), and 2,6-ST, as a pair of diastereoisomers at the newly formed cysteine stereocenter. The process proceeds in high yield and with complete retention of the alpha-anomeric configuration.

Separation of diastereomers of flavanone‐7‐O‐glycosides by capillary electrophoresis using sulfobutyl ether‐β‐cyclodextrin as the selector

AbstractA method was developed for the separation of diastereomers of flavanone‐7‐O‐glycosides by capillary electrophoresis using sulfobutyl ether‐β‐cyclodextrin (SBE‐β‐CD) in the background electrolyte. The effect of the concentration of the CD additive, buffer pH, and organic modifier on the migration times and resolution for five flavanone glycosides (naringin, hesperidin, neohesperidin, narirutin, and eriocitrin) was studied. Baseline separations of these compounds as pairs of diastereoisomers were achieved with 20 mM tetraborate buffer at pH 7 containing 5 mg/mL of SBE‐β‐CD and 10% (v/v) of methanol. The developed method was used for the qualitative analysis of the diastereomeric composition of the major flavanone glycosides in different citrus juices. The ability of SBE‐β‐CD to discriminate flavanone enantiomers was also investigated.

Dynamic chirality: keen selection in the face of stereochemical diversity in mechanically bonded compounds.

The template-directed syntheses, employing bisparaphenylene-[34]crown-10 (BPP34C10), 1,5-dinaphthoparaphenylene-[36]crown-10 (1/5NPPP36C10), and 1,5-dinaphtho-[38]crown-10 (1/5DNP38C10) as templates, of three [2]catenanes, whereby one of the two bipyridinium units in cyclobis(paraquat-p-phenylene) is replaced by a bipicolinium unit, are described. The crude reaction mixtures comprising the [2]catenanes all contain slightly more of the homologous [3]catenanes, wherein a "dimeric" octacationic cyclophane has the crown ether macrocycles encircling the alternating bipyridinium units with the bipicolinium units completely unfettered. X-ray crystallography, performed on all three [2]catenanes and two of the three [3]catenanes reveals co-conformational and stereochemical preferences that are stark and pronounced. Both the [3]catenanes crystallize as mixtures of diastereoisomers on account of the axial chirality associated with the picolinium units in the solid state. Dynamic (1)H NMR spectroscopy is employed to probe in solution the relative energy barriers for rotations by the phenylene and pyridinium rings in the tetracationic cyclophane component of the [2]catenanes. Where there are co-conformational changes that are stereochemically "allowed", crown ether circumrotation and rocking processes are also investigated for the relative rates of their occurrence. The outcome is one whereby the three [2]catenanes containing BPP34C10, 1/5NPPP36C10, and 1/5DNP38C10 exist as one major enantiomeric pair of diastereoisomers amongst two, four, and eight diastereoisomeric pairs of enantiomers, respectively. The diastereoisomerism is a consequence of the presence of axial chirality together with helical and/or planar chirality in the same interlocked molecule. These [2]catenanes constitute a rich reserve of new stereochemical types that might be tapped for their switching and mechanical properties.

Structural variations across the lanthanide series of macrocyclic DOTA complexes: insights into the design of contrast agents for magnetic resonance imaging.

It was early shown that the macrocyclic Ln(DOTA) complexes (DOTA = 1,4,7,10-tetra-azacyclododecane-N,N',N' ',N' "-tetraacetic acid) exists in solution as a mixture of two enantiomeric pairs of diastereoisomers differing in the ligand conformation, namely, square antiprismatic (SA) and twisted square antiprismatic (TSA) geometries, respectively. Later, extensive (1)H NMR investigations suggested that a coordination change may be superimposed on this conformational equilibrium involving two additional structures in which the metal ion possesses a coordination number of eight (CN 8). It was predicted that these two species, lacking the apical coordinated water molecule, would maintain the SA and TSA coordination geometries, and therefore, they have been labeled as SA' and TSA', respectively. In this work we report the X-ray solid-state crystal structure determination of six Ln(DOTA) complexes representative of all four coordination geometry typologies deduced from NMR solution studies. A distinctive structural feature that discriminates SA (and SA') and TSA (and TSA') structures is represented by the twist angle between the two square planes of the antiprism, the basal four nitrogen, and the apical four oxygen planes. [Ce(DOTA)(H(2)O)](-) displays a TSA structural typology with a twist angle of 25 degrees and a Ce-O(water) distance of 2.59 A. The SA-type structure has been found in the case of complexes with Pr(III), Nd(III), and Dy(III), where the twist angle is 39, 39, and 38 degrees, respectively, and the metal-water oxygen distance varies significantly (Pr-O(w) 2.529 A; Nd-O(w) 2.508 A; and Dy-O(w) 2.474 A). [Tm(DOTA)](-) displays a TSA'-type structure with a twist angle of 24 degrees. As compared with the TSA structure of the corresponding Ce(III) complex, the Tm(III) complex shows an overall marked shrinkage of all metal-nitrogen and metal-oxygen distances (ca. 0.2 A), which reflects the contraction of the metal ionic radius across the series but also the effect associated with the decrease of the CN from 9 to 8. In [Sc(DOTA)](-), the even smaller ionic radius of Sc(III) shifts the geometry of the coordination cage to the more compact SA' typology with a twist angle of 41 degrees, a value very similar to that found in the SA structures of lanthanide(III) ions with CN 9. Finally, an investigation was made into the hydration spheres of the complexes with SA and TSA geometries to account for the experimental evidence of a markedly different rate of water exchange for the two isomeric structures. This is of fundamental importance to the understanding of the corresponding Gd(III) complexes as MRI contrast agents.

Micellar electrokinetic capillary chromatographic separation of diastereoisomers of podophyllum lignans at the C4 position

Seven pairs of diastereoisomers of podophyllum lignans at the C4 position, including three pairs of spin-labeled compounds, have been separated within 20 min by MEKC with 20mm sodium tetraborate-30mm SDS-10% (v/v) 2-propanol (pH 9.5–9.7) as running buffer. The migration behavior of the compounds was explained satisfactorily on the basis of on their polarity and geometry. The method can be used to identify the purity of the lignans, and to determine the C4−H configurations of the spin-labeled derivatives.

Identification of adducts derived from reactions of (1-chloroethenyl)oxirane with nucleosides and calf thymus DNA.

(1-Chloroethenyl)oxirane is a major mutagenic metabolite of chloroprene, an important large-scale petrochemical used in the manufacture of synthetic rubbers. The reactions of (1-chloroethenyl)oxirane with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, thymidine, and calf thymus DNA have been studied in aqueous buffered solutions. The adducts from the nucleosides were isolated by reversed-phase HPLC, and characterized by their UV absorbance and (1)H and (13)C NMR spectroscopic and mass spectrometric features. The reaction with 2'-deoxyguanosine gave one major adduct, N7-(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGI), and eight minor adducts which were identified as diastereoisomeric pairs of N1-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyguanosine (dGII, dGIII), N3,N7-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGIV, dGV), N7,N9-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGVI, dGVII), and N1,N7-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGVIII, dGIX). The reaction of 2'-deoxyadenosine with (1-chloroethenyl)oxirane gave two adducts: N1-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyadenosine (dAI) and N(6)-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyadenosine (dAII). The adduct dAII was shown to arise via a Dimroth rearrangement of adduct dAI. The HPLC analyses of the reaction mixtures of (1-chloroethenyl)oxirane with 2'-deoxycytidine and thymidine showed the formation of one major product in each reaction. The adduct from 2'-deoxycytidine was identified as N3-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyuridine (dCI) derived by alkylation at N-3 followed by deamination. The adduct from thymidine was identified as N3-(3-chloro-2-hydroxy-3-buten-1-yl)-thymidine (TI). Reaction of (1-chloroethenyl)oxirane with calf thymus DNA gave all of the adducts observed from the individual nucleosides except dGII and dGIII. However, there was selectivity for the formation of dGI and dCI. The adduct levels in DNA were 9,630 (dGI), 240 (dCI), 83 (dAI), 6 (dAII), and 28 (TI) pmol/mg DNA, respectively. The preferred formation of dCI may be relevant to chloroprene mutagenesis.

Supramolecular Fullerene Chemistry: A Comprehensive Study of Cyclophane‐Type Mono‐ and Bis‐Crown Ether Conjugates of C70.

The covalently templated bis-functionalization of C70, employing bis-malonate 5 tethered by an anti-disubstituted dibenzo[18]crown-6 (DB18C6) ether, proceeds with complete regiospecificity and provides two diastereoisomeric pairs of enantiomeric C70 crown ether conjugates, (±)-7a and (±)-7b, featuring a five o'clock bis-addition pattern that is disfavored in sequential transformations (Scheme 1). The identity of (±)-7a was revealed by X-ray crystal-structure analysis (Fig. 6). With bis-malonate 6 containing a syn-disubstituted DB18C6 tether, the regioselectivity of the macrocylization via double Bingel cyclopropanation changed completely, affording two constitutionally isomeric C70 crown ether conjugates in a ca. 1 : 1 ratio featuring the twelve (16) and two o'clock ((±)-15) addition patterns, respectively (Scheme 3). The X-ray crystal-structure analysis of the twelve o'clock bis-adduct 16 revealed that a H2O molecule was included in the crown ether cavity (Figs. 7 and 8). Two sequential Bingel macrocyclizations, first with anti-DB18C6-tethered (5) and subsequently with syn-DB18C6-tethered (6) bis-malonates, provided access to the first fullerene bis-crown ether conjugates. The two diastereoisomeric pairs of enantiomers (±)-28a and (±)-28b were formed in high yield and with complete regioselectivity (Scheme 9). The cation-binding properties of all C70 crown-ether conjugates were determined with the help of ion-selective electrodes (ISEs). Mono-crown ether conjugates form stable 1 : 1 complexes with alkali-metal ions, whereas the tetrakis-adducts of C70, featuring two covalently attached crown ethers, form stable 1 : 1 and 1 : 2 host-guest complexes (Table 2). Comparative studies showed that the conformation of the DB18C6 ionophore imposed by the macrocyclic bridging to the fullerene is not particularly favorable for strong association. Reference compound (±)-22 (Scheme 4), in which the DB18C6 moiety is attached to the C70 sphere by a single bridge only and, therefore, possesses higher conformational flexibility, binds K+ and Na+ ions better by factors of 2 and 20, respectively. Electrochemical studies demonstrate that cation complexation at the crown ether site causes significant anodic shifts of the first reduction potential of the appended fullerene (Table 3). In case of the C70 mono-crown ether conjugates featuring a five o'clock functionalization pattern, addition of 1 equiv. of KPF6 caused an anodic shift of the first reduction wave in the cyclic voltammogram (CV) by 70 to 80 mV, which is the result of the electrostatic effect of the K+ ion bound closely to the fullerene core (Fig. 14). Addition of 2 equiv. of K+ ions to C70 bis-crown ether conjugates resulted in the observation of only one redox couple, whose potential is anodically shifted by 170 mV with respect to the corresponding wave in the absence of the salt (Fig. 16). The synthesis and characterization of novel tris- and tetrakis-adducts of C70 are reported (Schemes 5 and 6). Attempts to prepare even more highly functionalized derivatives resulted in the formation of novel pentakis- and hexakis-adducts and a single heptakis-adduct (Scheme 7), which were characterized by 1H- and 13C-NMR spectroscopy (Fig. 10), as well as matrix-assisted laser-desorption-ionization mass spectrometry (MALDI-TOF-MS). Based on predictions from density-functional-theory (DFT) calculations (Figs. 12 and 13), structures are proposed for the tris-, tetrakis-, and pentakis-adducts.

New crystalline complex of quinine and quinidine.

A new complex of diastereoisomeric pair, quinine and quinidine (QQd), was obtained from a mixture of saturated ethanol solutions of quinine and quinidine (0.5:1). The complex crystallises in the triclinic system, space group P1, and contains two molecules of quinine, two molecules of quinidine and four water molecules in the asymmetric unit. The X-ray structure analysis of a single crystal revealed that quinine and quinidine molecules occur in the so-called open conformation, characteristic for Cinchona alkaloids, whenever they are engaged in intermolecular hydrogen bonds. Quinine and quinidine molecules are organized in two very similar kinds of chains. In each chain the links that contain 14-membered rings can be distinguished. Within these rings quinine and quinidine molecules interact via intermolecular hydrogen bonds between the quinuclidine nitrogens and hydroxyl groups, mediated by water molecules. The links are connected with each other by hydrogen bonds between water molecules and nitrogens of the quinoline moieties, which interact via pi-pi stacking. The architecture of the hydrogen bond system in QQd, compared to those observed in the crystal structures of nonhydrated quinidine, cinchonine and cinchonidine, reveals the effect of the co-crystallizing water on the molecular packing. In nonhydrated alkaloid structures the hydrogen-bonded molecules form helical chains, different from those observed in the hydrated QQd complex and hydrated quinine toluene solvate (QTol). Comparison of QQd structure with that of QTol suggests that while the intermolecular hydrogen bonds in the system quinine-water-quinidine-water are very similar to those in quinine-water-quinine-water system, the mode of pi-pi interaction between their quinoline moieties depends on the absolute configuration of the interacting alkaloid molecules.

Supramolecular Fullerene Chemistry: A Comprehensive Study of Cyclophane-Type Mono- and Bis-Crown Ether Conjugates of C70

The covalently templated bis-functionalization of C70, employing bis-malonate 5 tethered by an anti-disubstituted dibenzo[18]crown-6 (DB18C6) ether, proceeds with complete regiospecificity and provides two diastereoisomeric pairs of enantiomeric C70 crown ether conjugates, (±)-7a and (±)-7b, featuring a five o'clock bis-addition pattern that is disfavored in sequential transformations (Scheme 1). The identity of (±)-7a was revealed by X-ray crystal-structure analysis (Fig. 6). With bis-malonate 6 containing a syn-disubstituted DB18C6 tether, the regioselectivity of the macrocylization via double Bingel cyclopropanation changed completely, affording two constitutionally isomeric C70 crown ether conjugates in a ca. 1 : 1 ratio featuring the twelve (16) and two o'clock ((±)-15) addition patterns, respectively (Scheme 3). The X-ray crystal-structure analysis of the twelve o'clock bis-adduct 16 revealed that a H2O molecule was included in the crown ether cavity (Figs. 7 and 8). Two sequential Bingel macrocyclizations, first with anti-DB18C6-tethered (5) and subsequently with syn-DB18C6-tethered (6) bis-malonates, provided access to the first fullerene bis-crown ether conjugates. The two diastereoisomeric pairs of enantiomers (±)-28a and (±)-28b were formed in high yield and with complete regioselectivity (Scheme 9). The cation-binding properties of all C70 crown-ether conjugates were determined with the help of ion-selective electrodes (ISEs). Mono-crown ether conjugates form stable 1 : 1 complexes with alkali-metal ions, whereas the tetrakis-adducts of C70, featuring two covalently attached crown ethers, form stable 1 : 1 and 1 : 2 host-guest complexes (Table 2). Comparative studies showed that the conformation of the DB18C6 ionophore imposed by the macrocyclic bridging to the fullerene is not particularly favorable for strong association. Reference compound (±)-22 (Scheme 4), in which the DB18C6 moiety is attached to the C70 sphere by a single bridge only and, therefore, possesses higher conformational flexibility, binds K+ and Na+ ions better by factors of 2 and 20, respectively. Electrochemical studies demonstrate that cation complexation at the crown ether site causes significant anodic shifts of the first reduction potential of the appended fullerene (Table 3). In case of the C70 mono-crown ether conjugates featuring a five o'clock functionalization pattern, addition of 1 equiv. of KPF6 caused an anodic shift of the first reduction wave in the cyclic voltammogram (CV) by 70 to 80 mV, which is the result of the electrostatic effect of the K+ ion bound closely to the fullerene core (Fig. 14). Addition of 2 equiv. of K+ ions to C70 bis-crown ether conjugates resulted in the observation of only one redox couple, whose potential is anodically shifted by 170 mV with respect to the corresponding wave in the absence of the salt (Fig. 16). The synthesis and characterization of novel tris- and tetrakis-adducts of C70 are reported (Schemes 5 and 6). Attempts to prepare even more highly functionalized derivatives resulted in the formation of novel pentakis- and hexakis-adducts and a single heptakis-adduct (Scheme 7), which were characterized by 1H- and 13C-NMR spectroscopy (Fig. 10), as well as matrix-assisted laser-desorption-ionization mass spectrometry (MALDI-TOF-MS). Based on predictions from density-functional-theory (DFT) calculations (Figs. 12 and 13), structures are proposed for the tris-, tetrakis-, and pentakis-adducts.

Separation of diastereoisomers of podophyllum lignans by micellar electrokinetic chromatography

Seven pairs of diastereoisomers of podophyllum lignans at 2-position, including two pairs of spin-labeled compounds, were separated by micellar electrokinetic chromatography with 5 m M sodium tetraborate–20 m M NaH 2PO 4–120 m M sodium dodecylsulfate–30% (v/v) 2-propanol (pH 6.5–7) within 35 min. The migration behaviors of the compounds with different types and concentrations of organic modifiers were studied. The method can be used to identify the purification of the lignans, monitor the 2-H configuration transformation, and determine the 2-H configuration of the spin-labeled derivatives.

General model of assignment of the relative stereochemistry in the Nicholas reaction products resulting from chiral dicobalthexacarbonyl‐1‐alkoxy‐propargylium cations

AbstractThe Nicholas reaction of chiral 1‐alkoxy‐dicobalthexacarbonyl‐propargylium cations with linear and/or cyclic silyl enol ethers resulted in the formation of two pairs of diastereoisomers (syn‐1, syn‐2 and anti‐1, anti‐2), depending on the relative stereochemistry of the two new stereocenters formed in the reaction products. Here, we present a model to establish the relative stereochemistry of those stereocenters on the basis of a correlation of their 1H and 13C NMR spectra, together with their conformational analysis and a study of the stereoelectronic interactions conditioning the chemical shifts and coupling constants. The importance of this method is based on its applicability to the assignment of the relative stereochemistry of non‐separable components of a diastereomeric mixture or, when diastereomers are non‐crystallizable oily products, not suitable for X‐ray diffraction analysis. Copyright © 2002 John Wiley & Sons, Ltd.

A novel C-C bond formation reaction with 1-methoxymethylindolylborate.

The reaction of 1-methoxymethylindolylborates 2 with electrophiles in the presence of benzaldehyde enabled the novel construction of tri-substituted indoles in a 'one-pot' procedure.

Molecular mechanics (MM3) study of the conformations of ethyl esters of diastereoisomeric 3-substituted 4,4,4-trichloro-2-cyano-butanoic acids

Molecular mechanics calculation (MM3 force field) were used to study the conformations of diastereoisomeric pairs of ethyl esters of 3-substituted 4,4,4-trichloro-2-cyano-butanoic acids in order to test an assumption from 1H NMR spectra about their preferred conformations. On the basis of the most probable preferred conformation in each case, an assignment of the relative configurations of these newly synthesized compounds was made in the earlier study. The present computed most favorable conformations are in accord with the earlier qualitative considerations in all cases, thus validating the assignment of the configurations of the diastereoisomers made previously.

Synthesis, characterization and reactions of cluster complexes containing SeRuCoM (M=Mo or W) core and a functionally substituted cyclopentadienyl ligand

Reactions of monoanions {M(CO) 3[η 5-C 5H 4C(O)CH 2CH 2CO 2Me]} − with RuCo 2(CO) 9(μ 3-Se) in THF at 60°C gave two new cluster derivatives (μ 3-Se)CoMRu(CO) 8[η 5-C 5H 4C(O)CH 2CH 2CO 2Me] (M=Mo 1, M=W 2). Similarly, reactions of dianions −{M(CO) 3[(η 5-C 5H 4)C(O)CH 2CH 2C(O)(η 5-C 5H 4)](CO) 3M} − with two molecules of RuCo 2(CO) 9(μ 3-Se) gave 1,4-succinoyl(biscyclopentadienyl)-bridged double cluster complexes (μ 3-Se)CoMRu(CO) 8[(η 5-C 5H 4)C(O)CH 2CH 2C(O)(η 5-C 5H 4)]CoMRu(CO) 8(μ 3-Se) (M=Mo 3, M=W 4). Treatment of cluster (μ 3-Se)CoMoRu(CO) 8[(η 5-C 5H 4)C(O)Me] with ammine derivatives 2,4-dinitrophenylhydrazine, NH 2NHC(S)NH 2, (−)-5-(α-phenyl)semioxamazide and l-(+)-menthydrazide, respectively, at room temperature produced four new hydrazone cluster derivatives (μ 3-Se)CoMoRu(CO) 8[η 5-C 5H 4C(NR)Me] (R=NHC 6H 3-2,4-(NO 2) 2 5, R=NHC(S)NH 2 6, R=NHC(O)C(O)NHCH(Me)(C 6H 5) 7, R=NHCO 2-menthyl 8). However, cluster 1 can only react with 2,4-dinitrophenylhydrazine to give the formation of cluster (μ 3-Se)CoMoRu(CO) 8[η 5-C 5H 4C(NR)CH 2CH 2CO 2Me] (R=NHC 6H 3-2,4-(NO 2) 2 9) under similar condition. Although, two kinds of optically active groups have been introduced into cluster (μ 3-Se)CoMoRu(CO) 8[(η 5-C 5H 4)C(O)Me], the mixture of diastereoisomers could not be separated by silica gel chromatography. The 13C-NMR spectra showed the presence of a pair of diastereoisomers.