Synthese von tri- und tetrasaccharid-einheiten des O-antigens aus Aeromonas salmonicida

The following oligosaccharide sequences containing the repeating unit of the O-specific chain of lipopolysaccharides from aeromonas salmonicida have been synthesized: α-D-Glcp-(1→3)-α-L-Rhap-(1 →3)-β-D-ManpNAcO(CH₂)₈CO₂Me, α-D-Glcp-(1 →4)-α-D-Glcp-(1→3)-α-L-Rhap-(1→3)-β-D-ManpNAcO(CH₂)₈CO₂Me and α-D-Glcp(1→4)-α-D-Glcp-(1→3)-[β-D-ManpNAc(1→4)]-L-Rha.     

Synthesis of haloconduritols from an endo-cycloadduct of furan and vinylene carbonate

A method for preparing haloconduritols having a conduritol-A construction is described. A mixture of endo- and exo-cycloadduct derivatives prepared from the Diels-Alder reaction of furan and vinylene carbonate was converted into diacetate derivatives by hydrolysis (K₂CO₃/MeOH) followed by acetylation (Ac₂O/pyridine). Boron trihalide (BBr₃ or BCl₃)-assisted ring-opening of the endo-diacetate in CH₂Cl₂ at −78°C gave (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol 1,2-diacetate from which the corresponding triacetate was prepared by acetylation (AcCl). trans-Esterification of the triacetate (MeOH/HCl) afforded (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol (X=Br or Cl). BF₃-Assisted ring-opening of the endo-diacetate in CH₂Cl₂ gave (1α,2α,3β,6β)-6-chloro-4-cyclohexene-1,2,3-triol 1,2-diacetate by means of halogen exchange.     

How To Stabilize or Break β-Peptidic Helices by Disulfide Bridges: Synthesis and CD Investigation of β-Peptides with Cysteine and Homocysteine Side Chains

all-L -β³-Penta-, hexa-, and heptapeptides with the proteinogenic side chains of valine, leucine, serine, cysteine, and methionine have been prepared by previously described procedures ( 12 , 13 , 14 , 15 ; Schemes 2 – 5). Thioether cleavage with Na/NH₃ in β-HMet residues has also provided a β³-hexapeptide with homocysteine (CH₂CH₂S) side chains ( 13e ). The HS−(CH₂)_n groups were positioned on the β-peptidic backbone in such a way that, upon disulfide-bridge formation, the corresponding β-peptide was expected to maintain either a 3₁-helical secondary structure ( 1 , 2 ) (Fig. 1) or to be forced to adopt another conformation ( 3 , 4 ). The 13-, 17-, 19-, and 21-membered-ring macrocyclic disulfide derivatives and their open-chain precursors, as well as all synthetic intermediates, were purified (crystallization, flash or preparative HPL chromatography; Fig. 5) and fully characterized (m.p., [α]_D, CD, IR, NMR, FAB or ESI mass spectroscopy, and elemental analysis, whenever possible; Fig. 2 and Exper. Part). The structures in MeOH and H₂O of the new β-peptides were studied by CD spectroscopy (Figs. 3 and 4), where the characteristic 215-nm-trough/200-nm-peak pattern was used as an indicator for the presence or absence of (M)-3₁-helical conformations. A CH₂−S₂−CH₂ and, somewhat less so, a (CH₂)₂−S₂−(CH₂)₂ bracket between residues i and i+3 ( 1 vs. 12d , and 2 vs. 13e in Fig. 3) give rise to CD spectra which are compatible with the presence of 3₁-helical structures, while CH₂−S₂−CH₂ brackets between residues i and i+2 ( 3 vs. 14c ) or i and i+4 ( 4 vs. 15c in Fig. 4) do not.     

SYNTHESIS OF 2′-DEOXY-2′-FLUORO- 1-β-d-ARABINOFURANOSYL URACIL DERIVATIVES: A METHOD SUITABLE FOR PREPARATION OF [18F]-LABELED NUCLEOSIDES

ABSTRACT

N-glycosylation of 2,4-bis-O-(trimethylsilyl)-pyrimidine bases with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-1-(Br, OBz)-α-d-arabinose derivatives are reported. 1-Bromo-arabinose provides high yield and a favorable anomeric ratio (β/α) of pyrimidine nucleoside in either MeCN or CH₂Cl?CH₂Cl. This method should be suitable for the synthesis of 2′-deoxy-2′-[¹⁸F]fluoro-1-β-d-arabinofuranosyluracil derivatives.     

Über triterpene—XXIX : Zur struktur des avenacins

From the roots of oat (Avena sativa) a second antibiotic active glycoside, avenacine B, was isolated in addition to the main glycoside avenacine A. In the aglycone of A the double bond could not be established contrary to the statement in the literature but an aldehyde group in addition to the keto group was identified and therefore the proposed structure has to be revised. In the aglycone of B the —CH₂OH-group of A has been substituted by CH₃. The structures of the sugar chains in both glycosides have been determined, in avenacine A as [β-d-gluco-pyranosyl(1 → 4)-[β-d-glucopyranosyl (1 → 2)]-α-l-arabinosyl (1)- and in B as [β-d-glucopyranosyl (1 → 4)]-β-d-glucopyranosyl (1)-.     

Actinide-centered cyclometalation chemistry. An unusually distorted thorium bishydrocarbyl: Thp[η5-(CH3)5C5]2CH2Si(CH3)3]2

The crystal and molecular structure of the complex Th[η⁵-(CH₃)₅C₅]₂[CH₂-Si(CH₃)₃]₂, which undergoes facile intramolecular cyclometalation to the thoracyclobutane Th[η⁵-(CH₃)₅C₅]₂(CH₂)₂Si(CH₃)₂, is reported. While the Th[η⁵-(CH₃)₅C₅]₂ ligation is unexceptional, the Th[CH₂Si(CH₃)₃]₂ fragment is highly unsymmetrical having Th-C (corresponding angle Th-C-Si) 2.51(1) Å (132.0(6)°) and 2.46(1) Å (148.0(7)°). This conformation, which appears to result from severe intramolecular non-bonded contacts, allows a methyl hydrogen atom of one CH₂Si(CH₃)₃ ligand to approach within ca. 2.3 Å of the α-carbon atom of the other CH₂Si(CH₃)₃ ligand.     

Über die Reaktion des käfigartigen Kieselsäurederivats [(CH3)2HSi]8Si8O20 mit ungesättigten organischen Verbindungen

Reaction of the Cage-like Silicic Acid Derivative [(CH₃)₂HSi]₈Si₈O₂₀ with Unsaturated Organic Compounds By ²⁹Si, ¹H, and ¹³C NMR investigations were shown that the eight HSi?groups of the double four-ring silicic acid derivative [(CH₃)₂HSi]₈Si₈O₂₀ react with the following unsaturated compounds: vinylcyclohexene, allyl glycidyl ether, methyl methacrylate, octadecene-1, and styrene. The resulting oily products are soluble in organic solvents. The compounds were characterized by the chemical shifts of the ²⁹Si, ¹H, and ¹³C NMR signals. Their formulae are [C₆H₉(CH₂)₂Si(CH₃)₂]₈Si₈O₂₀, [CH₃OOCCH(CH₃)CH₂Si(CH₃)₂]₈Si₈O₂₀, [CH₃(CH₂)₁₇Si(CH₃)₂]₈Si₈O₂₀ and [C₆H₅(CH₂)₂Si(CH₃)₂]₈Si₈O₂₀, and [C₆H₅CH(CH₃)Si(CH₃)₂]₈ Si₈O₂₀, respectively. Mainly the addition reactions do not follow the Markovnikov rule.     

Monocyclic,Substituted Imidazoles as Glycosidase Inhibitors

A range of 4‐monosubstituted and 2,4‐disubstituted 1H‐imidazoles and 1H‐imidazole‐1‐ethanols (R C(4): CH₂CH₂Ph, CHOHCH₂Ph, Ph, or Me; R C(2): CH₂OH, CHOHCH₂OH, CN, or CH₂NHAc) were prepared and tested as inhibitors of α‐ and β‐glucosidases and of a β‐galactosidase. A new access to 4‐(2‐phenylethyl)‐1H‐imidazoles starting from 4‐phenylbutan‐1‐ol was elaborated. The strongest inhibitors are the 2‐substituted 4‐(2‐phenylethyl)‐1H‐imidazoles 24a and 26a (R C(2): CH₂OH and CHOHCH₂OH) and the 2‐phenylethanol 34 . They inhibit the β‐galactosidase from bovine liver and the β‐glucosidase from Caldocellum saccharolyticum with inhibition constants in the micromolar range, but do not inhibit the α‐glucosidase from brewer's yeast.     

The synthesis of hexahydro-6H-dibenzo[b,d]pyrans: Derivatives of 9-Nor-9β-hydroxyhexahydrocannabinol

To assess the importance of the phenol functionality in cannabinoids for analgetic activity a new series of 9-nor-9β-hydroxyhexahydrocannabinoids was prepared. The synthesis of 1-substituted (H, CH₂OH, OH, NH₂) 6aβ,7,8,9,10,10aα-hexahydro-9β-hydroxy-6,6-dimethyl-3-[1-methyl-4-phenylbutoxy]-6H-dibenzo[b,d]pyrans from 3,5-dihydroxystilbene, 3,3′,5,5′-tetrahydroxystilbene or 1,3,5-trihydroxybenzene is described. Relative stereochemistry and structure confirmations were obtained by nmr and X-ray crystal analysis.     

Synthesis and proposed conformations of l-prolyl-l-leucyl-β-alanine alkylamides

The synthesis of H-Pro-Leu-β-Ala-NH₂, H-Pro-Leu-β-Ala-NHCH₃ and H-Pro-Leu-β-Ala-N(CH₃)₂ is described. On the basis of IR and ¹H NMR spectral data, a 7-membered ring including the NH of β-alanine with the CO of proline should be assigned for the H-Pro-Leu-β-Ala-N(CH₃)₂. Consequently, the plausible conformations for H-Pro-Leu-β-Ala-NH₂ and H-Pro-Leu-β-Ala-NHCH₃ derive from the formation of an 11-membered ring, between the trans amide proton and the CO of Pro, or from the formation of an 8-membered ring, between this carboxamide proton and the CO of Leu, plus the aforementioned 7-membered ring.     

Synthesis of new α,α,β,β-tetrafluoroesters

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical conditions to give the corresponding adducts, which underwent elimination reaction to give β-vinyl and β-allyl α,α,β,β-tetrafluoroesters, CH₂CHCF₂CF₂CO₂Et, 4 and CH₂CHCH₂CF₂CF₂CO₂Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with copper or palladium complex, followed by reduction to remove iodine to produce ω-alkenyl-α,α,β,β-tetrafluoroester CH₂CH(CH₂)₄CF₂CF₂CO₂Et 6 and α,α,β,β-tetrafluoroester C₄H₉CH₂CHICF₂CF₂CO₂Et.     

Nucleoside und Nucleotide,Teil 12. Synthese von Dinucleosidmonophosphaten mit 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1H)-pyrimidon als Baustein

Nucleosides and Nucleotides. Part 12. Synthesis of Dinucleoside Monophosphates Containing 1-(2′-Deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidone The connexion of the modified nucleoside 1-(2′-deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidone (M_d, 2 ) with the natural nucleotides pT_d and pG_d is described. The protected dinucleoside monophosphates (MeOTr)M_dpT_d ( 6 ) and (MeOTr)M_dpG ( 9 ) were prepared by the standard phosphodiester method using DCC as condensing agent. M_dpT_d ( 7 ) was obtained by treatment of 6 with formic acid/methanol 7 : 3 at 0° 9 was converted to the free dinucleoside monophosphate M_dpG_d ( 11 ) by removing the N-isobutyryl- and p-methoxytrityl protecting group on consecutive treatment with 0.04N CH₃ONa in CH₃OH and HCOOH/CH₃OH 7:3 at 0° respectively. Enzymatic degradation of the free dinucleoside of the free dinucleoside monophosphates 7 and 11 yielded the corresponding nucleosides and nucleotides in the correct ratios.     

Vibrational spectra of ethyl iodedes

The infrared spectra of CH₃CH₂I, CD₃CH₂I, and CH₃CD₂I of the vapors and the solids at 170°C have been recorded from 4000-200 cm^?1. The Raman spectra of the liquids and vapors have also been recorded and depolarization values have been measured. Assignment of the eighteen fundamental vibrations has been based on depolarization values, band contours, group-frequency correlations, and normal coordinate calculations. A critical discussion of the CH stretching assignments in CH₃CH₂X molecules is presented.     

Total synthesis of the sesquiterpene (±)-hirsutene using an organoselenium-mediated cyclization reaction

Cyclization of 2-carbomethoxy-3-(4',4'-dimethylcyclopent-2-enylmethyl)cyclopentanone (4) with N-phenylselenophthalimide and tin(IV) chloride affords cis-syn-cis-1β-carbomethoxy-4,4-dimethyl-3β-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (8) and cis-anti-cis-1β-carbomethoxy-4,4-dimethyl-3α-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (9). Both of these selenides can be elaborated to cis-anti-cis-4,4-dimethyl-1β-methyltricyclo [6.3.0.0^2,6]undecan-11-one (13) which upon treatment with CH₂Br₂/ TiCl₄/Zn affords the sesquiterpene (±)-hirsutene (1) in 20% overall yield.     

1,5-Migrations of silicon between oxygen centers in silyl β-diketones

A series of acyclic silyl diketonates, (CH₃)₃Si(dik), where dik = dipivaloyl-methanate, diisobutyrylmethanate and hexafluoroacetylacetonate, along with a new series of cyclic acetylacetonates of the type CH₃(-CH₂(CH₂)_xCH₂-)Si(acac), where x = 1, 2, and 3, have been shown to possess enol ether structures in which the acyl group is positioned cis or trans to the silyl group. The ratios of cis to trans configurations in the (CH₃)₃Si(dik) series increase from <0.02 to >50.0 in the order of diketonate substituents CF₃ < CH₃ <i-C₃H₇ < t-C₄H₉. The ratios for the CH₃(-CH₂(CH₂)xCH₂-)Si(acac) compounds increases in the order χ = 1 > 2 > 3. These data are interpreted in terms of incipient pentacoordination of silicon by the carbonyl oxygen atom in the cis isomer. Rates of 1,5-migration of silicon between oxygen centers in the cis isomers have been determined by NMR spectroscopy. The dependence of the rearrangement rates on diketonate substituent and angle strain at silicon indicate that the migration process is better viewed as an internal nucleophilic displacement, rather than a sigmatropic shift. 1,5-Migration in the chiral (C₆H₅CH₂)(CH₃)(C₆H₅)Si derivative of dipivaloylmethanate occurs exclusively with retention of configuration at silicon. The large difference in activation energy for migration and inversion (>18 kcal/mol) precludes the possibility of distinguishing between a stepwise and concerted displacement mechanism.     

Radiative decay of vibrationally excited CH2-

We have observed the presence of vibrationally excited CH₂^- created in a discharge, by measuring the photodetachment from CH₂^- as it radiatively relaxes in a high vacuum ion trap. We used a tunable IR laser to produce photons with energies above and below the expected threshold for removing an electron from the ground state. The time dependence of the photodetachment is consistent with the electron affinity of 5250 cm^-1 (0.65 eV) obtained by Sears and Bunker for the ground state X?³B₁ methylene. We have tentatively assigned radiative lifetimes for the excited bending vibrations of CH₂^-:600 ±300 msec for v₂ = 1,80±40msec for v₂ = 2, and 10± 5 msec for v₂ = 3.     

Synthesis of Oligosaccharides Designed to form Micelles,Corresponding to Structures Found in Ovarian Cyst Fluid

ABSTRACT

The syntheses of α-D-GlcpNAc-(1→4)-β-D-Galp-(1→4)-β-D-GlcNAc-(1→O)-(CH₂)₁₅CH₃ (1) and fragments thereof, corresponding to structures found in human ovarian cyst fluid, are described. Silver triflate promoted coupling of 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-glucopyranosyl bromide (12) and galactose acceptor (11) gave a disaccharide donor (13), which was readily transformed into the corresponding bromo-derivative 18. For the synthesis of disaccharide β-D-Galp-(1→4)-D-GlcNAc, several differently protected glucosamine acceptors were prepared. It was found that cetyl alcohol needed to be introduced after the formation of the β-galactoside bond. Glycosylation of pent-4-enyl 3,6-di-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D-glucopyranoside (30) with (3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-benzoyl-α-D-galactopyranosyl bromide (18) by use of silver triflate as promoter gave the desired trisaccharide 31. Finally 31 was transformed via coupling to the long alkyl chain aglycon and deprotection into the title compound 1.     

Arsenic-containing ribofuranosides and dimethylarsinic acid in green seaweed,Codium fragile

Three water-soluble arsenic compounds were isolated from the green seaweed Codium fragile. These compounds were identified as 1-glycerophosphoryl-2-hydroxy-3-[5′-deoxy-5′-(dimethylarsinoyl)-β-ribofuranosyloxy]propane (1a), 1′ -(1,2-dihydroxypropyl)-5′ -deoxy-5′ -(dimethylarsinoyl)-β-ribofuranoside (1b), and dimethylarsinic acid ((CH₃)₂AsOOH). The structures of these compounds were ascertained by ¹H NMR spectroscopy. Compounds 1a and 1b accounted for 60 % and dimethylarsinic acid for 5% of the water-soluble arsenic.     

螺桨烷型分子BX[(CH_2)_n]_3和BX(CH_2)[CH(CH_2)_nCH](X=N,P)的结构和性质

采用密度泛函理论(DFT)研究了螺桨烷型分子BX[(CH2)n]3和BX(CH2)[CH(CH2)n CH](X=N,P;n=1-6)的结构、稳定性、化学键和电子光谱性质.计算结果表明这些分子都是稳定的.BX[(CH2)n]3(X=N,P;n=1-6)的最高占据分子轨道(HOMO)和最低空分子轨道(LUMO)之间的能隙均大于5.20 eV,其中BN[CH2]3和BP[CH2]3的能隙超过7.0 eV,与C5H6的能隙(7.27 eV)很接近,BX(CH2)[CH(CH2)n CH](X=N,P;n=1-6)的能隙在6.80 eV左右.所研究分子能量的二阶差分表明BN[(CH2)3]3、BP[(CH2)4]3及BX(CH2)[CH(CH2)2CH](X=N,P)是最稳定的.BX[(CH2)n]3的Wiberg键级表明除了BN[(CH2)n]3(n=2和6)中不存在B―N键,其它化合物中B和N均形成了化学键,BP[(CH2)n]3中除了BP[(CH2)2]3不存在B―P键,其它的均存在.电子密度的拓扑分析表明N―B键属于离子键,而P―B键具有共价键特征.BX[(CH2)n]3(X=N,P)的第一垂直激发能分别在191.1-284.8 nm和191.8-270.1 nm之间,BX(CH2)[CH(CH2)n CH](X=N,P)的第一垂直激发能分别在190.5-199.7 nm和209.0-221.3 nm之间.     

Chemical Transformations of 4,6-Dimethyl-2β-hydroxy-8-oxo-3,5,7-trioxatetracyclo[7.2.1.04,11.06,10]dodecane

Reactions of 4,6-dimethyl-2β-hydroxy-8-oxo-3,5,7-trioxatetracyclo-[7.2.1.0.^4,11.0^6,10]dodecane 1 with nucleophiles have been studied. Reaction of 1 with alcohols, triethylsilane, allyltrimethylsilane, and methylthiotrimethylsilane in CH₂Cl₂ in the presence of TiCL₄, gave the substitution products 2,7a, 7b, and 7c in 80-90% yields. The substitution reaction took place chemoselectively on the hemiacetal group of I. Reaction of 1 with cyanotrimethylsilane in CH₂C1₂ in the presence of TiCL₄, gave compound 8 and the rearranged product 9. The structure of 9 was proven by X-ray analysis.