Showing papers in "Helvetica Chimica Acta in 1991"
TL;DR: In this article, the synthesis of enantiomerically pure, C2-symmetric 4,4′, 5,5,5′-tetrahydro-2,2′-methylenebis[oxazoles] and 4, 4′, 4.5, 6.5, 5, 5, 6.2, 2,2, 2.2, 1.
Abstract: The synthesis of a series of enantiomerically pure, C2-symmetric 4,4′,5,5′-tetrahydro-2,2′-methylenebis[oxazoles] and 4,4′,5,5′-tetrahydro-2,2′-bi(oxazoles) is reported. Copper complexes with anionic tetrahydromethylenebis[oxazole] ligands are efficient catalysts for the enantioselective cyclopropane formation from olefins and diazo compounds (up to 96% ee in the reaction of styrene with menthyl diazoacetate). Tetrahydrobi(oxazole)iridium(I) complexes were found to catalyze transfer hydrogenations of aryl alkyl ketones with i-PrOH (up to 91% ee). Tetrahydrobi(oxazole)palladium complexes can be used as enantioselective catalysts for allylic nucleophilic substitution (up to 77% ee in the reaction of PhCHCHCH(OAc)Ph with NaHC(COOMe)2).
402 citations
TL;DR: In this paper, axially dissymmetric diphosphines (R)- and (S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenymethylphosphine) ((R)-and(S)-5a; ‘MeO-BIPHEP’) and the analogues (R-and (S-5b and 5c) have been synthesized in enantiomerically pure form.
Abstract: The new axially dissymmetric diphosphines (R)- and (S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenyl phosphine) ((R)- and (S)-5a; ‘MeO-BIPHEP’) and the analogues (R)- and (S)-5b and 5c have been synthesized in enantiomerically pure form. These ligands have become readily available by a synthetic scheme which employs, as key steps, an ortho-lithiation/iodination reaction of the (m-methoxyphenyl)diprienylphosphine oxides 8 and a subsequent Ullmann reaction of the resulting iodides 9 to provide the racemic bis(phosphine oxides) 10. The bis(phosphine oxides) 10 subsequently are resolved with (−)-(2R,3R)- and (+)-(2S,3S)-O-2,3-dibenzoyltartaric acid and reduced to diphosphines 5. The Ullmann reaction constitutes a new and efficient route to 2,2′-bis(phosphinoyl)-substituted biphenyl systems. Absolute configurations were established for (R)-5a by X-ray analysis of the derived Pd complex (R,R)-17a, and for 5b and 5c by means of 1H-NMR comparisons of the derived Pd complexes 16 or 17, respectively, and by means of CD comparisons. The MeO-BIPHEP diphosphine 5a proved to be as efficient as the previously described BIPHEMP diphosphine ((6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine)) in enantioselective isomerizations and hydrogenations.
241 citations
TL;DR: In this paper, the chiral tris, and pentakis(bipyridine) ligand strands 3a and 4 were synthesized, each in optically pure form with (S,S)-configuration.
Abstract: The chiral tris, and pentakis(bipyridine) ligand strands 3a and 4 were synthesised, each in optically pure form with (S,S)-configuration. Ligand 3a yielded substituted double-helical metal complexes, derived from the parent trihelicate structure 2, with CuI and AgI ions. The spectral data, in particular the 1H-NMR spectra and the large positive Cotton effect, indicate that helicate formation occurs with very high induction of helicity. Together with consideration of the steric effects in the two possible helical diastereoisomers (P)-1 and (M)-1 that may be formed, the data favour the preferential generation of the right-handed double helicate (P)-1 from the tris(bipyridine) strand 3a of(S,S)-configuration.
180 citations
TL;DR: In this paper, the authors treated methyl 2-(1-hydroxyalkyl)prop-2-enoates with conc. HBr solution and transformed them regioselectively into N-substituted methyl (E)-2- (aminomethyl)alk-2 -enoates 3 (SN2 reaction) and into Nsubstitized methyl 2(1-aminoalkyl), 2(2)-prop-1-hexamino-alkyl, 2-(2)-enoates 4(SN2′ reaction.
Abstract: Treatment of methyl 2-(1-hydroxyalkyl)prop-2-enoates 1 with conc. HBr solution afforded methyl (Z)-2-(bromomethyl)alk-2-enoates 2, which were transformed regioselectively into N-substituted methyl (E)-2- (aminomethyl)alk-2-enoates 3 (SN2 reaction) and into N-substituted methyl 2-(1-aminoalkyl)prop-2-enoates 4(SN2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the SN2 reaction occurring in MeCN and the SN2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β-lactams 7 and 8, containing an exocyciic alkylidene and methylidene group at C(3), respectively.
149 citations
TL;DR: Diazo transfer from trifluoromethanesulfonyl azide (TfN3) to 2-amino-2-deoxy-glycoses constitutes a high-yielding, simple procedure for the preparation of partially protected or unprotected 2-azido- 2- deoxy-aldoses.
Abstract: Diazo transfer from trifluoromethanesulfonyl azide (TfN3) to 2-amino-2-deoxy-glycoses constitutes a high-yielding, simple procedure for the preparation of partially protected or unprotected 2-azido-2-deoxy-aldoses. Thus, the D-allosamine derivative 2 gave 93% of 3, while diazo transfer to D-glucosamine, D-mannosamine, and D-galactosamine, followed by acetylation, yielded the azides 5, 7, and 9 in yields of 74–91, 65, and 70%, respectively.
135 citations
TL;DR: The 1H-phenalen-1-one (1) has been shown to be one of the most efficient singlet-oxygen sensitizers in both polar and non-polar media, in particular in the area of relatively high energies of excitation as mentioned in this paper.
Abstract: The efficiency of aromatic ketones as singlet-oxygen (1O2(1Δg)) sensitizers can vary considerably with the electronic configuration of their lowest triplet state and the solvent used. Near-infrared measurements of tie luminescence of singlet oxygen have shown that the quantum yield of singlet-oxygen production (ΦΔ) by 1H-phenalen-1-one (1) is close to unity in both polar (ΦΔ = 0.97±0.03 in methanol) and non-polar solvents (ΦΔ = 0.93±0.04 in benzene). Analysis of the absorption spectra of the ground state and phosphorescence measurements show that the lowest singlet and triplet states have dominant π, π* electronic configurations. The quantum yield of intersystem crossing (ΦISC) of 1, determined by laser flash photolysis (partial-saturation method), is equal to unity. In comparison with other aromatic ketones, these parameters are important for the discussion of the surprisingly high ΦISC of 1 and the efficient energy transfer from its triplet state to molecular oxygen. The 1H-phenalen-1-one (1), being one of the most efficient singlet-oxygen sensitizers in both polar and non-polar media, could be used as a reference sensitizer, in particular in the area of relatively high energies of excitation.
135 citations
TL;DR: A number of biologically relevant O4-phospho-L-tyrosine-containing peptides have been synthesized by either the global phosphorylation of the side-chain-unprotected L-Tyrosine moiety in presynthesized resin-bound peptides or alternatively by the incorporation of suitably protected O4/L/L building blocks in the continuous-flow method of Fmoc solid-phase peptide synthesis.
Abstract: A number of biologically relevant O4-phospho-L-tyrosine-containing peptides have been synthesized by either the global phosphorylation of the side-chain-unprotected L-tyrosine moiety in presynthesized resin-bound peptides or alternatively by the incorporation of suitably protected O4-phospho-L-tyrosine building blocks in the continuous-flow method of Fmoc solid-phase peptide synthesis. Different phosphate-protecting groups have been applied.
115 citations
TL;DR: In this article, the preparation of a 3:1 complex of hydroquinone and C60, (HQ)3C60, is reported and its X-ray crystal structure described.
Abstract: The preparation of a 3:1 complex of hydroquinone (HQ) and C60, (HQ)3C60, is reported and its X-ray crystal structure described. The HQ host builds up a single H-bonded super-polonium network with super-cubes as building blocks, which accommodate the large C60 guest molecules. The enclathration of C60 is rather tight (high density of the complex) owing, in part, to favorable charge-transfer host-guest interactions (π-donor-acceptor complex). Nonetheless, the C60 molecules arc orientationally disordered, and no individual bond lengths could be measured. In contrast, the HQ host network is essentially ordered and well-defined with normal intramolecular geometry. No appreciable (powder) conductivity could be observed for (HQ)3C60, yet ESR spectra of single crystals showed interesting narrow signals.
101 citations
TL;DR: The tetrazole 1 is a new β-glucosidase inhibitor (IC50=8·10−5M, Emulsin), obtained (92%) by deprotection of 22, the product of an intramolecular cycloaddition of the azidonitrile 20.
Abstract: The tetrazole 1 is a new β-glucosidase inhibitor (IC50=8·10−5M, Emulsin), obtained (92%) by deprotection of 22, the product of an intramolecular cycloaddition of the azidonitrile 20. This azidonitrile was formed as an intermediate by treating the L-ido-bromide 14 or the L-ido-tosylate 19 with NaN3 at 110–120°. It was isolated in a separate experiment. The yield of 22 from 19 reached 70%; 21 was formed as by-product (10%). The bromide 14 (42%) and the iodide 15 (30–35%) were obtained from the nitrile 13, together with the 2,5-anhydro-L-idononitrile 16, which was formed in ca. 35–45%. The tosylate 19 was obtained from 18 (97%). To obtain 18, the nitrile 13 was oxidized according to Swern (→17, 92%) and then reduced (NaBH4, CeCl3), leading to 18and 13 (92%, 18/13 93:7). Reduction of the tetrahydropyridotetrazole 22 with LiAlH4 afforded 83 % of the piperidine 23, which was deprotected to (+)-1-deoxynojirimycin hydroacetate (2·AcOH, 86%) and further converted into the corresponding hydrochloride and into the free base 2.
99 citations
TL;DR: The structure of a derivative of coenzyme F430 from methanogenic bacteria, the bromide salt of 12,13-diepi-F430 pentamethyl ester (5, X = Br), was determined by X-ray structure analysis as discussed by the authors.
Abstract: The structure of a derivative of coenzyme F430 from methanogenic bacteria, the bromide salt of 12,13-diepi-F430 pentamethyl ester (5, X = Br), was determined by X-ray structure analysis. It reveals a more pronounced saddle-shaped out-of-plane deformation of the macrocycle than any hydroporphinoid Ni complex investigated so far. The crystal structure confirms the constitution proposed for coenzyme F430 (2) and shows that in the epimer 5, the three stereogenic centers in ring D, C(17), C(18), and C(19), have the (17S)-, (18S)-, and (19R)-configuration, respectively. Deuteration and 2D-NMR studies independently demonstrate that native coenzyme F430 (2) has the same configuration in ring D as the epimer 5. Therefore, our original tentative assignment of configuration at C(19) and C(18) [1] has to be reversed. This completes the assignment of configuration for all stereogenic centers in coenzyme F430, which has the structure shown in Formula2.
97 citations
TL;DR: In this paper, the reaction of cyclosporin A with Lawesson's reagent under different conditions yields various thiocyclosporins, in which carbonyl O-atoms and/or the hydroxy O-atom of the MeBmt residue are replaced by an S-atom.
Abstract: The reaction of cyclosporin A (CsA) with Lawesson's reagent under different conditions yields various thiocyclosporins, in which carbonyl O-atoms and/or the hydroxy O-atom of the MeBmt residue are replaced by an S-atom. The position of the S-atom is determined by NMR spectroscopy, and the conformations of the products are studied by NMR spectroscopy and X-ray crystallography. Some of the thiocyclosporins show interesting conformational properties. Whereas one conformation strongly dominates for CsA in CDCL3, two conformers A and B, in a ratio 58:42 are found for [1ψ2, CS–NH]CsA. Extensive NMR studies including new 2D and 3D heteronuclear techniques and restrained MD calculations using ROE effects demonstrate that the major conformer A is identical to CsA, while the minor conformer B contains an additional cis peptide bond between the Sar3 and MeLeu4 residues. [4ψ5, CSNH; 7ψ8, CS–NH]CsA exhibits a conformation very similar to crystalline CsA. However, the D-Ala8NH, MeLeu6Co γ-turn H-bond is not present in this dithio analogue. Also different is the MeBmt1side-chain conformation, the dithio conformation showing a strong MeBmt1OH, Sar3CO H-bond. Immunosuppressive activities of thiocyclosporins are measured in IL-2 and IL-8 reporter gene assays. Their activities are discussed in relation to their conformations.
TL;DR: The crystal structures of four inclusion compounds of 2,6-dimethylideneadamantane-1,3,5,7-tetracarboxylic acid (4) are described in this paper.
Abstract: The crystal structures of four inclusion compounds of 2,6-dimethylideneadamantane-1,3,5,7-tetracarboxylic acid (4) are described, which involve the following guest species: (a) a mixture of 4-methylpent-3-en-2-one, 2,6-dimethylhepta-2,5-dien-4-one, and mesitylene (condensation products of acetone); (b) mesitylene; (c) a mixture of 4-methylpent-3-en-2-one and mesitylene; (d) (tert-butyl)benzene. In all four cases, the host architectures consist of two interpenetrating super-diamond networks built up by the tetra-acid molecules via pairwise H-bonds between the tetrahedrally directed COOH groups. In the first three cases (tetragonal crystal symmetry), the two diamond-like host lattices interpenetrate symmetrically, in the fourth case (monoclinic) asymmetrically. This asymmetry is brought about by the increased steric bulk of the (tert-butyl)benzene guest molecules. Attempts to enforce an inclusion compound of 4 with a single, extremely hollow diamond-like host lattice by offering still bulkier guest molecules have as yet not been met with success. The generally very high propensity of 4 to form inclusion compounds was envisaged and designed beforehand by appropriate evaluation and modulation of the crystal structure of the parent adamantane-1,3,5,7-tetracarboxylic acid, which represents a fivefold diamond-like self-inclusion compound. Crystals of the free, uncomplexed 4 appear to be extremely unstable and could so far not be obtained. On the other hand, from aqueous solution a very stable monohydrate of 4 may be crystallized (4-H2O), which was also subjected to X-ray analysis. The (triclinic) crystal structure of 4·H2O involves an interesting dichotomy inasmuch its pattern of H-bonding may be rationalized either in terms of a double, cross-linked super-zincblende (sphalerite) architecture, or as a system of porous, puckered 4-connected sheets, which interpenetrate each other pairwise and are cross-linked by the H2O molecules. Various structure and (space group) symmetry characteristics of the supramolecular solid-state complexes reported here are highlighted by pointing out analogies with comparable structures retrieved from the literature.
TL;DR: The bridged bis(dihydrooxazole) compound (−)-2 and its silylated derivative (−)-3 have been synthesised as building blocks for chiral ligands as discussed by the authors.
Abstract: The bridged bis(dihydrooxazole) compound (−)-2 and its silylated derivative (−)-3 have been synthesised as building blocks for chiral ligands. The complex of (−)-3 with Cu II has been obtained, and its crystal structure has been determined. The Cu II ion is bound to two deprotonated ligands in a twisted tetracoordinated geometry
TL;DR: In this article, the Europium cryptates of the new macrobicyclic ligands 2 and 3 incorporating the 2,2′-bipyri dine 1,1′-dioxide and 3,3′-biisoquinoline 2, 2′ -dioxide units, respectively, have been prepared.
Abstract: The sodium and europium cryptates of the new macrobicyclic ligands 2 and 3 incorporating the 2,2′-bipyri dine 1,1′-dioxide and 3,3′-biisoquinoline 2,2′-dioxide units, respectively, have been prepared. The EuIII complexes present characteristic 1H-NMR spectra, showing large shifts, and are strongly luminescent in aqueous solution. These markedly improved luminescent properties, compared to the europium cryptate of the parent macrobicyclic ligand 1, may be ascribed at least in part to a better shielding of the bound cation by the N-oxide sites.
TL;DR: In this article, a mixture of the amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and LiBr (preferably 0,5 and 5 equiv., resp.) turns out to be a highly efficient catalyst for saponifications (in THF/H2O) and transesterification (in ROH).
Abstract: A mixture of the amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and LiBr (preferably 0,5 and 5 equiv., resp.) turns out to be a highly efficient catalyst (at 0–25°) for saponifications (in THF/H2O) and transesterifications (in ROH). The scope and limitations of the method are determined using ca. two dozens of different ester/alcohol combinations (Schemes 2 and 3). The investigation is focused on peptides as substrates. Under carefully controlled conditions, no epirnerization occurs with N-Boc- and N-Z-protected peptide esters, when methyl, ethyl, isopropyl, or allyl esters are the products, as shown for peptides containing up to six amino acids, with Ala, Len MeLeu, Asp(OEt), or Tyr at the C-terminus (Scheme 3 and Tables 1 and 2). Hydrolytic and transesterifying detachments of Boc-Leu-Ala-Gly-Val-OR and Boc-Leu-Ala-Gly-Phe-OR (R = H, Me) from PAM and Wang resins (1–8 h at 0–25°, 2 equiv. of DBU, 5 equiv. of LiBr) can be achieved by this method without epimerization of the C-terrninal stereogenic center; a comparison with other methods (HF, Ti(OR)4) is given (Schemes 4 and 5). Possible protecting-group strategies involving the DBU/LiBr method are discussed (Table 3), Extensive experimental details are given.
TL;DR: In this paper, a general strategy for the synthesis of oligobipyridine ligands 2-5 containing from two to five 2,2′-bipyrine subunits for helical metal complexes is described.
Abstract: A general strategy for the synthesis of oligobipyridine ligands 2–5 containing from two to five 2,2′-bipyridine subunits, for helical metal complexes is described (sec Scheme). Both the unsubstituted parent strands (a series) as well as their derivatives bearing fester or amide functions in the 4,4′-positions of the bipyridine moieties (b–d series) have been obtained.
TL;DR: In this paper, the synthesis of the phospha analogue 10 of DANA was described, which is a strong inhibitor of the Vibrio cholerae sialidase.
Abstract: The synthesis of the phospha analogue 10 of DANA (2) is described. Bromo-hydroxylation of the known 11 ( 12 and 13) followed by treatment of the major bromohydrin 13 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the oxirane 14 (Scheme 1). Depending on the solvent, TiBr4 transformed 14 into 16 or into a 15/16 mixture. Reductive debromination of 16 ( 17), followed by benzylation provided 18. Oxidattve decarboxylation (Pb(OAc)4) of the acid, obtained by saponification of 18, yielded the anomeric acetates 19 and 20. While 19 was inert under the conditions of phosphonoylation, the more reactive imidate 22, obtained together with 23 from 19/20via21 (Scheme 2), gave a mixture of the phosphonates 24/25 and the bicyclic acetal 26. Debenzylation of 24/25 and acetylation led to the acetoxyphosphonates 27/28. Since β-elimination of AcOH from 27/28 proved difficult, the bromide 34 was prepared from 27/28 by photobromination and subjected to reductive elimination with Zn/Cu ( 35; Scheme 3). This two-step sequence was first investigated using the model compounds 30 and 31. Transesterification of 35, followed by deacetylation gave 10, which is a strong inhibitor of the Vibrio Cholerae sialidase.
TL;DR: In this article, the tripeptide and hexapeptide derivatives Boc-Gly-Sar-MeLeu-OH (5b) and 12b can be poly-deprotonated (tri- and pentalithio derivatives K and P, respectively), and thus C-alkylated on sarcosine (Sar) moieties with MeI and allyl or PhCH2Br.
Abstract: The tripeptide and hexapeptide derivatives Boc-Gly-Sar-MeLeu-OH (5b), Boc-Ala-Sar-Sar-OH (6b), Boc-Ala-Sar-MeLeu-OH (7b), and Boc-Abu-Sar-MeLeu-Val-MeLeu-Ala-OH (12b) can be poly-deprotonated (tri- and pentalithio derivatives K and P, respectively), and thus C-alkylated on sarcosine (Sar) moieties with MeI and allyl or PhCH2Br. The polylithiated species are solubilized in THF, and their reactivity modified by excess base (lithium diisopropylamide (LDA)), by added LiCl, and/or the cosolvent N,N′-dimethylpropyleneurea (DMPU). Optimization of the reaction conditions for methylation in the cases of 7b (Table 3) and 12b (Scheme 8) gave products in which the Sar residue of the educt has been transformed into a Me-D-Ala unit in yields of 80 (9c/8c) and 67% (14c/13c), respectively, and with a diastereoselectivity of ca. 4:1. Less selective methylations and benzylations were observed with the tripeptides 5b and 6b containing only one stereogenic center; also, excess base and alkyl halide may lead to double alkylations in those latter two cases (Tables 1 and 2). No epimerization of stereogenic centers was detected under the strong-base conditions. The analysis of the products was accomplished by a combination of NMR and FAB-MS spectroscopy, as well as by hydrolysis to the parent amino acids, subsequent formation of derivatives with isopropyl isocyanate, and GC analysis on the chiral column Chirasil-Val®.
TL;DR: In this paper, the 9-(2′-deoxy-a-D-threo-pentofuranosyl)adenine was protected at its 6-NH2 group with cither a benzoyl (5a) or a (dimethyfamino)methylidcnc (6a) residue and with a dimethoxytntyl group at 5′-OH (5b, 6b).
Abstract: The 9-(2′-deoxy-a-D-threo-pentofuranosyl)adenine (=9-(2′-deoxy-a-D-xylofuranosyl)adeninc, xAd; 2) was protected at its 6-NH2 group with cither a benzoyl (5a) or a (dimethyfamino)methylidcnc (6a) residue and with a dimethoxytntyl group at 5′-OH (5b, 6b). Compounds 5b and 6b were then converted into the 3′-phosphonates 5c and 6c; moreover, the 2-cyanoethyl phosphoramidite 6d was synthesized starting from fib. The DNA building blocks were used for solid-phase synthesis of d[(xA)122-A] (8). The latter was hybridized with d[(xT)12-T] (Tm = 35°); in contrast, with d(T12), complex formation was not observed. Moreover, xAd and xTd were introduced into the self-complementary dodccamcr d(G-T-A-G-A-A-T-T-C-T-A-C) (12) at different positions lo give the oligomcrs 13–16. All oligonucleotides were characterised by temperature-dependent CD and UV spectroscopy, and in addition, 14 by T-jump experiments. From concentration-dependent Tm measurements, the thermodynamic paraneters of the melting as well as the tendency of hairpin formation of the oligonucleotides were deduced. Oligemer 14 was hydrolyzed by snake-venom phosphodiesterase in a discontinuous way implying a fast hydrolysis of unmodified 3′- and 5′-flanks followed by a slow hydrolysis of the remaining modified tetramer. In contrast to this, oligonucleotide 16 was hydrolyzed in a continuous reaction. In both cases, calf-spleen phosphodiesterase hydrolyzed the oligomer only marginally.
TL;DR: The feed-induced biosynthesis of 1 and 2 in leaves of the Lima bean Phaseolus lunatm infested with the spider mite Tetranychus urticae probably requires a preceding release of nerolidol or geranyllinalool from phylogenic glycosides prior to the fragmentation reaction.
Abstract: In higher plants, the two homotcrpenes 4,8-dimethylnona-l,3,7-triene (1) and 4,8,12-trimethyltrideca-1,3,7,11-teiracnc (2) originate from nerolidol (3) or geranyllinalool (4) by anoxidative cleavage of their C-skele-lons. The reaction proceeds with exclusive loss of H8–C(5) of 3 and formal production of a C4 fragment. The site specificity of the enzyme(s) is identical for all of the hitherto examined plant families (Agavaceae, Asclepiadaceae, Asteraceae, Leguminosae, Magnoliaceae, and Saxifragaceae). The enzyme tolerates a wide range of structural modifications at the polar head of 3. Instead of 3, also gcranylacclone 12 and the secondary alcohol 13 can be cleaved to the homoterpene 1 and as yet unidentified carbonyl fragments. The CC bonds within the aliphatic chain of 3 seem to be essential for the oxidative bond cleavage as well as for recognition and embedding of the substrate into the active center of the enzyme(s). The feed-induced biosynthesis of 1 and 2 in leaves of the Lima bean Phaseolus lunatm infested with the spider mite Tetranychus urticae probably requires a preceding release of nerolidol (3) or geranyllinalool (4) from phylogenic glycosides prior to the fragmentation reaction. The microbial reduction of the trienoic acids 6 and 6ais the key stop for the synthesis of deuterium labelled nerolidol (3RS,5R)-and (3RS,5S)-9.
TL;DR: In this article, the synthesis of 2-deoxyisoguanosine (2), and the pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]-pyridine 2-Deoxyribonucleosides 3 and 4 is described.
Abstract: The synthesis of 2′-deoxyisoguanosine (2), and the pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine 2′-deoxyribonucleosides 3 and 4 is described. Condensation of the imidazole precursor 5 with benzoyl isocyanate followed by reaction with ammonia gave 2. Its N(7) regioisomer was obtained from 6. Compound 2 was also prepared by the photochemically induced conversion of 2-Chloro- and 2-bromopurine 2′-deoxyribofuranosides 9a and 10, respectively, in aqueous solution, The photo reaction was further used for the synthesis of the compounds 3 and 4 starting with the amino-chloro-2′-deoxynucleosides 9b and 9c, respectively.
TL;DR: In this article, a route for synthesizing C-nucleosides with 2,6-substituted pyridines as heterocyclic aglycones is described.
Abstract: A route for synthesizing C-nucleosides with 2,6-substituted pyridines as heterocyclic aglycones is described. Condensation of appropriately substituted lithiated pyridines with ribono-1,4-lactone derivatives yields hemiacetal 4a–g (Table 1), which can be reduced by Et3SiH and BF3·Et2O to the corresponding C-nucleoside (see Scheme 1 for 4d β-D-5). Conditions are presented that optimize the amount of the 2,6-dichloropyridine-derived β-D-anomer β-D-5 formed (Table 3). Aminolysis of β-D-5 yields the diaminonucleoside 14 (Scheme 3).
TL;DR: In this paper, the prepn. of the optically pure tritertiary phosphine (RRR)-I is reported, and the x-ray crystal structure of I and its norbornadienerhodium complex are reported.
Abstract: The prepn. of the optically pure tritertiary phosphine (RRR)-I is reported. The route followed involves deprotonation of optically pure (R)-P(BH3)Me(CMe3)Ph, the reaction of the resulting carbanion with MeSiCl3, followed by removal with morpholine of the BH3-protecting groups from the tritertiary phosphine-borane (RRR)-MeSi[CH2P(BH3)(CMe3)Ph]3. The x-ray crystal structure of I and its norbornadienerhodium complex are reported. Furthermore, sepn. of the racemic phosphine-borane can be conveniently carried out by using medium-pressure liq. chromatog. with cellulose triacetate as a chiral stationary phase. [on SciFinder(R)]
TL;DR: The course of peptide coupling reactions as well as the swelling properties of a peptide-resin are influenced by the addition of inorganic salts (LiCl, LiBr, LiClO 4, KSCN) as mentioned in this paper.
Abstract: The course of solid-phase peptide-coupling reactions as well as the swelling properties of a peptide-resin are influenced by the addition of inorganic salts (LiCl, LiBr, LiClO 4 , KSCN). Used as additives, these salts can: 1) improve coupling yields (e.g., for Fmoc-(ALa) 5 -Phe-resin→Fmoc-(Ala) 6 -Phe-resin in DMF/CH 2 Cl 2 1:1 from 89.4 to 97.1% (for poly(ethylene oxide) on polystyrene (=PEO-PS) resin) or from 77.5 to 93.8% (for poly-(N,N'-dimethylaylamide) on «Kieselgur» (=PDMAA-KG) resin) without and with 0.4 M LiCl, respectively); 2) increase resin swelling (e.g. for Fmoc-(Ala) 5 -Phe-(polystyrene resin) from 2.42 to 5.71-fold in 1-methylpyrrolidin-2-one (=NMP) without and with LiCl, respectively); and 3) change coupling rates. Examples of coupling reactions and swelling behaviour (degree and rate) in different solvent (DMF, DMF/CH 2 Cl 2 1:1, THF, NMP, N,N-dimethylpropyleneurea (=DMPU) with and without salts) using different resins (polystyrene (PS); PEO-PS, and PDMAA-KG) and an improved analysis of alanine oligomers up to Ala 12 -Phe by HPLC and FAB-MS are reported
TL;DR: In this article, an enzyme is extracted from the red peel of Amanita muscaria which cleaves the C(2)−C(3) and C(4)-C(5) bond of the aromatic ring of L-dopa to form a mixture of 4,5-secodopa and 2,3-secoda.
Abstract: An enzyme is extracted from the red peel of Amanita muscaria which cleaves the C(2)–C(3) and the C(4)–C(5) bond of the aromatic ring of L-dopa (1) to form a mixture of 4,5-secodopa (= salt of 6-amino-2-hydroxy-4-(2′-oxoethylidene)hept-2-enedioic acid; 2) and 2,3-secodopa ( = salt of 7-amino-5-formyl-2-hydroxyocta-2,4-dienedioic acid; 3), two hitherto hypothetical biosynthetic intermediates (see Scheme). Though isolation of these products has not been possible, structural evidence is inferred from reaction products, kinetics, and spectroscopical characteristics in comparison with known compounds. Secodopas 2 and 3 are characterized in dilute solution by HPLC and UV/VIS spectroscopy (anions; λmax 424 and 414 nm, resp., ϵ420 = 25500; on acidification, shift to 380 and 372 nm, resp.). They cyclize without enzyme catalysis, optimally at pH 4.5–5; 3 produces muscaflavin (5) and 2 betalamic acid (4). The products arc identified by direct comparison with authentic samples in HPLC, by 1H-NMR of 5, and by condensation of 4 with L-proline to form the well known betalain indicaxanthin (7). The enzymatic conversion of L-dopa (1) via2 to betalamic acid (4; (S)) and its condensation with L-proline leads to pure natural indicaxanthin (7; (2S,115)); correspondingly, the enzymatic conversion of D-dopa to (R)-betalamic acid and its condensation with L-proline produces isoindicaxanthin ((2S,11R)) which is unknown in nature. Particularly relevant is the fact that the same enzyme cleaves pyrocatechol to produce a solution of the enolate form of the known 2-hydroxy-6-oxohexa-2,4-dienoate (secopyrocatechol; 9; see Fig. 5). Dissociation constants of the corresponding enolic functions in the cleavage products are determined by spectrometric titration and compared to those of known systems.
TL;DR: In this article, the synthesis of 1n-3n-phospholipids for two-dimensional crystallization of progesterone and estradiol receptors was reported.
Abstract: The synthesis of phospholipids 1n–3n, rationally designed for two-dimensional crystallization of progesterone and estradiol receptors, is reported. The structure of these lipids provides them with essential properties such as fluidity and stability when spread into monolayers at the air/H2O interface, affinity for the protein to be crystallized, and accessibility of the ligand under the lipid monolayer.
TL;DR: A paramagnetic CD3-NiII derivative 5b of the pentamethyl ester 2 (F430M) of coenzyme F430 was prepared by in situ methylation with (CD3)2Mg and characterized by its isotropically shifted 2H-NMR spectrum.
Abstract: A methylnickel(II) derivative of coenzyme F430 (1) was proposed as an intermediate in the enzymic process catalyzed by methyl-CoM reductasc. Indirect evidence points to formation of CH3–F430MII in the reaction of F30M1 (obtained from F430MII (2)) with eleclrophilic methyl donors. The results presented here show, that such a compound does exist. A paramagnetic CD3–NiII derivative 5b of the pentamethyl ester 2 (F430M) of coenzyme F430 was prepared by in situ methylation with (CD3)2Mg and characterized by its isotropically shifted 2H-NMR spectrum. At −40°, the very broad D-signal of the axially coordinated CD3 group is found at −490 ppm. Comparison with the 2H- and 1H-NMR spectra of mcthyl(tetramethylcyclam)nickel(II) derivatives 4 ([NiII(CH3))(tmc)]CF3SO3 (4a) is the only isolated CH3–Ni derivative of a N4macrocyclic NiII complex' shows that the large isotropic shift to high field is characteristic for a Me group axially bound to the Ni center. The temperature dependence of the isotropic shift of the CD3–Ni group in both 4b and 5b follows Curie's law and yields 2H hyperfine coupling constants of −0.65 (4b) and −0.85 MHz (5b), respectively. The 1H-NMR spectrum indicates that, in contrast to the five-coordinate monochloro complex [NiIICl(tmc)]+, intermolecular exchange of the axial ligand in [NiII(CH3)(tmc)]+4a is either slow at the NMR time scale or does not occur at all.
TL;DR: In this paper, a combination of two-dimensional NMR techniques was used to completely assign the 1H- and 13C-NMR chemical shifts of the two configurational isomers resulting from the cis-trans isomerization about the single amide bond.
Abstract: The potent immunosuppressant drug FK506 (2) has been examined by 1H- and 13C-NMR spectroscopy and NOE-restrained molecular dynamics to elucidate the conformation in solution. A combination of two- and three-dimensional NMR techniques was used to completely assign the 1H- and 13C-NMR chemical shifts of the two configurational isomers resulting from the cis-trans isomerization about the single amide bond. Hetero- and homonuclear coupling constants were measured to assign the diastereotopic methylene protons at C(16), C(18), and C(23). Intramolecular HH distances were defined from NOESY spectra recorded at −30° in CDCl3 and used as constraints in molecular-dynamics simulations. The conformational preferences of 2 in solution are discussed in light of the constitutional features recently proposed to be necessary for binding and activity.
TL;DR: In this article, the synthesis of the complexes of various metals ligated to chiral 4,5-dihydro-2-(2′-oxidophenyl-ϰO)oxazoles was described.
Abstract: The synthesis of the complexes 3 of various metals ligated to chiral 4,5-dihydro-2-(2′-oxidophenyl-ϰO)oxazoles-ϰN is described (Scheme). Three of them, i.e.3a, 3e, and 3f containing CuII, ZnII and NiII, respectively, were analyzed by X-ray diffraction studies. A series of CuII complexes (6a–d) with differently substituted dihydrooxazoles have been synthesized.
TL;DR: In this paper, the acylnitroso dienophile was assumed to be in the s-cis conformation in the transition state, the approach of the diene being endo.
Abstract: The C 2 -symmetrical chiral pyrrolidines 2 and 3 are of opposite helicity. The corresponding N-acylnitroso dienophiles 6 and 7 react in good yield with cyclohexadiene, leading thereby with excellent diastereoisomeric excess to the expected Diels-Alder cycloadducts (see Scheme). The [2.2.2] bicyclic moieties of the major diastereoisomers 9 and 11 proved to be of opposite configuration, as expected. Their configuration is best explained by assuming the acylnitroso dienophile to be in the s-cis conformation in the transition state, the approach of the diene being endo (see Fig.)