1-Methoxy-, 1-deoxy-11-hydroxy- and 11-Hydroxy-1-methoxy-Δ-tetrahydrocannabinols: new selective ligands for the CB2 receptor

Three series of new cannabinoids were prepared and their affinities for the CB₁ and CB₂ cannabinoid recptors were determined. These are the 1-methoxy-3-(1′,1′-dimethylalkyl)-, 1-deoxy-11-hydroxy-3-(1′,1′-dimethylalkyl)- and 11-hydroxy-1-methoxy-3-(1′,1′-dimethylalkyl)-Δ⁸-tetrahydrocannabinols, which contain alkyl chains from dimethylethyl to dimethylheptyl appended to C-3 of the cannabinoid. All of these compounds have greater affinity for the CB₂ receptor than for the CB₁ receptor, however only 1-methoxy-3-(1′,1′-dimethylhexyl)-Δ⁸-THC (JWH-229, 6e) has effectively no affinity for the CB₁ receptor (K_i=3134±110 nM) and high affinity for CB₂ (K_i=18±2 nM).     

Conformational properties of Eu(III) complexes of 3,3′; 5,3″-polymethylene bridged derivatives of 2,2′; 6,2″-terpyridine

The complex [Eu(tpy)₃](ClO₄)₃ where TPY=2,2′; 6,2″-terpyridine, has been prepared and reexamined. The complex appears to be stable in acetonitrile solution with respect to decomplexation of the ligands but the addition of water does cause partial replacement of tpy. Analogous complexes have been prepared with 3,3′; 5,3″-polymethylene bridged derivatives of tpy having two or three carbons in the bridge. The bridging enforces a cisoid geometry of the ligand and prohibits its replacement by added water. An X-ray determination was carried out for [Eu(3b)₃](ClO₄)₃, where 3b=3,3′; 5,3″-dimethylene tpy, which crystallizes in the monoclinic space group P2₁/c with a=11.908(4), b=15.768(5), c=29.513(9) Å, β=93.60(2)°, μ=13.5 cm⁻¹ and Z=4. The complex forms a tricapped trigonal prism with each of the ligands adopting the same dl conformation. Variable temperature NMR analysis of the bridged ligand complexes indicates that conformational inversion of the bound ligand is not a concerted process and barriers for inversion of individual methylene units can be estimated from coalescence of the signals from the geminal methylene protons. The luminescence properties of the bridged tpy complexes are similar to the parent unbridged system.     

2-(3′-Hydroxypropylidene)-1α-hydroxy-19-norvitamin D compounds with truncated side chains

Our recent studies with 2-(3′-hydroxypropylidene) analogs of 1α,25-dihydroxy-19-norvitamin D₃ showed that this 2-substituent creates compounds with very potent biological activity. In the continuing search for vitamin D compounds with selective activity profiles, we prepared a series of 1α-hydroxy-19-norvitamin D analogs characterized by the presence of a 3′-hydroxypropylidene substituent at C-2 and a truncated side chain. These vitamin D compounds were efficiently prepared using convergent syntheses. The C,D-fragments, namely the Grundmann ketones 19, 20, 27, 36 and 37 were synthesized from the known 8β-benzoyloxy-22-aldehydes 12 and 29. These hydrindanones were subjected to Lythgoe type Wittig–Horner coupling with phosphine oxide 21, prepared by us previously, and after hydroxyl deprotection the set of 19-norvitamins 7–11 was successfully obtained. According to our expectations, all analogs (with an exception of the 20R-compound 7) have pronounced in vitro activity. When compared to the natural hormone 1α,25-(OH)₂D₃ (1), they show the same or only slightly reduced affinity for the vitamin D receptor while being similarly effective as 1 in differentiation of HL-60 cells into monocytes.     

Structure and properties of a novel OH bridged dimetal helical complex with 6,6-dimethyl-2,2′:6′,2″:6″,2:6,2-quinquepyridine ligand

A new monohelical OH⁻ bridged dinuclear complex [Zn₂(dmqpy)(OOCCH₃)₂(μ-OH)][ClO₄] · 0.5EtOH, where dmqpy is 6,6-dimethyl-2,2′:6′,2″:6″,2:6,2-quinquepyridine, has been synthesized and characterized by X-ray crystallography: monoclinic, space group P2₁/c, a=13.670(1), b=14.751(1), c=16.782(1) Å, β=96.59(1)°, U=3361.7(4) ų, Z=4, R=0.0601. Two Zn(II) ions are in different coordination modes, one is five-coordinate with a N₃O₂ donor set and the other is N₂O₂ four-coordinate with a distorted tetrahedral geometry, and the zinc ions are bridged by a hydroxyl group. The presence of the OH⁻ bridge is further confirmed by electrospray mass and infrared spectroscopies. The solution properties of the complex were investigated by ¹H NMR spectroscopy. The results of NMR indicate that the complex has higher symmetry in solution than in the solid state.     

The X-ray structure analysis of bis-2,2′,N,N′-bipyridyl ketone cobalt(III) nitrate dihydrate

An X-ray structural analysis of bis-2,2′,N,N′-bipyridyl ketone cobalt(III) nitrate dihydrate, CoC₂₂H₂₀N₄O₄⁺· NO₃⁻·2H₂O,M_r=559.38 g/mol, P , a=8.862(2), b=16.195(3), c=8.772(2) Å, α=103.54(2), β=95.74(3), γ=105.07°, V=1164.4(4) ų, Z=2, D_x=1.595 g/cm³, Mo Kα radiation (λ=0.71073 Å), μ=7.8 cm⁻¹ and R=0.079, revealed a Co(III) cation in a slightly distorted octahedral environment. The structure reveals that the ligand di-2-pyridyl ketone (dpk) has undergone a hydration reaction across the ketone double bond and one of the hydrate oxygen atoms coordinated to the metal forming a tridentate chelate. This new Co(dpk-hydrate)₂⁺ complex displays the least distorted geometry yet reported for either 1:1 or 1:2 (metal:ligand) complexes. A geometry optimization using the INDO model Hamiltonian as implemented in the program ZINDO was performed on the title complex with the Co³⁺ modeled as a singlet. The result of the computation corroborates the geometry of the title complex as that expected for Co³⁺.     

PAF-antagonistic bicyclo[3.2.1]octanoid neolignans from leaves of Ocotea macrophylla Kunth. (Lauraceae)

Di-nor-benzofuran neolignan aldehydes, Δ⁷-3,4-methylenedioxy-3′-methoxy-8′,9′-dinor-4′,7-epoxy-8,3′-neolignan-7′-aldehyde (ocophyllal A) 1, Δ⁷-3,4,5,3′-tetramethoxy-8′,9′-dinor-4′,7-epoxy-8,3′-neolignan-7′-aldehyde (ocophyllal B) 2, and macrophyllin-type bicyclo[3.2.1]octanoid neolignans (7R, 8R, 3′S, 4′S, 5′R)-Δ⁸′-4′-hydroxy-5′-methoxy-3,4-methylenedioxy-2′,3′,4′,5′-tetrahydro-2′-oxo-7.3′,8.5′-neolignan (ocophyllol A) 3, (7R, 8R, 3′S, 4′S, 5′R)-Δ⁸′-4′-hydroxy-3,4,5′-trimethoxy-2′,3′,4′,5′-tetrahydro-2′-oxo-7.3′,8.5′-neolignan (ocophyllol B) 4, (7R, 8R, 3′S, 4′S, 5′R)-Δ⁸′-4′-hydroxy-3,4,5,5′-tetramethoxy-2′,3′,4′,5′-tetrahydro-2′-oxo-7.3′,8.5′-neolignan (ocophyllol C) 5, as well as 2′-epi-guianin 6 and (+)-licarin B 7, were isolated and characterized from leaves of Ocotea macrophylla (Lauraceae). The structures and configuration of these compounds were determined by extensive spectroscopic analyses. Inhibition of platelet activating factor (PAF)-induced aggregation of rabbit platelets were tested with neolignans 1–7. Although compound 6 was the most potent PAF-antagonist, compounds 3–5 showed some activity.     

Synthesis and magnetic properties of bis(μ-hydroxo)bis[(2,2 ′-bipyridyl)copper(II)] squarate. Crystal structure of bis(μ-hydroxo)bis[(2,2′-bipyridyl)copper(II)] squarate tetrahydrate

The compound [Cu₂(bipy)₂(OH)₂](C₄O₄)·5.5H₂O, where bipy and C₄O₄²⁻ correspond to 2,2′-bipyridyl and squarate (dianion of 3,4-dihydroxy-3-cyclo- butene-1,3-dione) respectively, has been synthesized. Its magnetic properties have been investigated in the 2–300 K temperature range. The ground state is a spin-triplet state, with a singlet-triplet separation of 145 cm⁻¹. The EPR powder spectrum confirms the nature of the ground state.Well-formed single crystals of the tetrahydrate, [Cu₂(bipy)₂(OH)₂](C₄O₄)·4H₂O, were grown from aqueous solutions and characterized by X-ray diffraction. The system is triclinic, space group P , with a = 9.022(2), b = 9.040(2), c = 8.409(2) Å, α = 103.51(2), β = 103.42(3), γ = 103.37(2)°, V = 642.9(3) ų, Z = 1, D_x = 1.699 g cm⁻³, μ(Mo Kα) = 17.208 cm⁻¹, F(000) = 336 and T= 295 K. A total of 2251 data were collected over the range 1θ25°; of these, 1993 (independent and with I3σ(I)) were used in the structural analysis. The final R and R_w residuals were 0.034 and 0.038 respectively. The structure contains squarato-O¹, O³-bridged bis(μ-hydroxo)bis[(2,2′-bipyridyl)copper(II)] units forming zigzag one-dimensional chains. Each copper atom is in a square-pyramidal environment with the two nitrogen atoms of 2,2′-bipyridyl and the two oxygen atoms of the hydroxo groups building the basal plane and another oxygen atom of the squarate lying in the apical position.The magnetic properties are discussed in the light of spectral and structural data and compared with the reported ones for other bis(μ-hydroxo)bis[(2,2′-bipyridyl)copper(II)] complexes.     

Solution structure investigations of olefin Pd(II) and Pt(II) complex ion pairs bearing α-diimine ligands by F, H-HOESY NMR

Complexes [M(η¹,η²-C₈H₁₂OMe)((2,6-(R)₂---C₆H₃)N=C(R′)---C(R′)=N((2,6-(R)₂---C₆H₃))]PF₆ (where M=Pd, R=H and R′₂=Me₂ (1), M=Pd, R=Me and R′₂=Me₂ (2), M=Pd, R=Et and R′₂=Me₂ (3), M=Pd, R=iPr and R′₂=Me₂ (4), M=Pd, R=iPr and R′₂=An (5), M=Pt, R=iPr and R′₂=An (6)) were synthesized by the reaction of [M(η¹,η²-C₈H₁₂OMe)Cl]₂ with the appropriate α-diimine ligand in the presence of NH₄PF₆. Their ion pair structure in solution was investigated by detecting dipolar interactions between protons belonging to the cation and fluorine nuclei of the anion (interionic contacts) in the ¹⁹F, ¹H-HOESY NMR spectra. In complexes 1–4, the anion in solution is located close to the peripheral protons of the α-diimine ligand and it interacts with the R′ protons and with the R protons that point toward the R′ groups. The steric protection of apical position exerted by the R substituents is clearly illustrated by the absence of interionic contacts between any protons of the cycloctenylmethoxy-moiety and the anion for R≥Me in 1–4. In complexes 5 and 6 the interactions between the anion and the peripheral N,N protons also predominate but other anion–cation orientations are significantly present and, consequently, the interionic structure is less specific.     

Derivatives of β- -fructofuranosyl α- -galactopyranoside

De-etherification of 6,6′-di-O-tritylsucrose hexa-acetate (2) with boiling, aqueous acetic acid caused 4→6 acetyl migration and gave a syrupy hexa-acetate 14, characterised as the 4,6′-dimethanesulphonate 15. Reaction of 2,3,3′4′,6-penta-O-acetylsucrose (5) with trityl chloride in pyridine gave a mixture containing the 1′,6′-diether 6 the 6′-ether 9, confirming the lower reactivity of HO-1′ to tritylation. Subsequent mesylation, detritylation, acetylation afforded the corresponding 4-methanesulphonate 8 1′,4-dimethanesulphonate 11. Reaction of these sulphonates with benzoate, azide, bromide, and chloride anions afforded derivatives of β- -fructofuranosyl α- -galactopyranoside (29) by inversion of configuration at C-4. Treatment of the 4,6′-diol 14 the 1,′4,6′-triol 5, the 4-hydroxy 1′,6′-diether 6 with sulphuryl chloride effected replacement of the free hydroxyl groups and gave the corresponding, crystalline chlorodeoxy derivatives. The same 4-chloro-4-deoxy derivative was isolated when the 4-hydroxy-1′,6′-diether 6 was treated with mesyl chloride in N,N-dimethylformamide.     

Purification of chemically synthesised dinucleoside(5′,5′) polyphosphates by displacement chromatography

Dinucleoside(5′,5′) polyphosphates (Ap_nA, Ap_nG, Gp_nG, n=3–6) are new group of hormones controlling important biological processes. Because some of the dinucleoside(5′,5′) polyphosphates are commercially not available purification of chemical synthesised dinucleoside(5′,5′) polyphosphates became necessary in order to test their physiological and pharmacological properties. It was the aim of this study to find a method which allows purification of 0.1–0.2 g quantities of dinucleoside polyphosphates by analytical HPLC columns yielding products with impurities lower than 1.0%. Adenosine(5′)-polyphospho-(5′)guanosines were synthesised by mixing the corresponding mononucleotides. The reaction results in a complex mixture of Ap_nA, Ap_nG and Gp_nG (with n=3–6 in all cases). The reaction mixture was concentrated on a preparative C₁₈ reversed-phase column. The concentrate was displaced on a reversed-phase stationary. As a result of displacement chromatography, anion-exchange chromatography in gradient modus yielded baseline separated dinucleoside polyphosphates (homogeneity of the fractions>99%). The identity of the substances were determined by matrix assisted laser desorption ionisation mass spectrometry.     

Cyclic 3′,5′-AMP phosphodiesterase in Physarum polycephalum: II. Kinetic properties

The effect of several inhibitors of the enzyme cyclic 3′,5′-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3′,5′-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3′,5′-AMP at concentrations as high as 1 · 10⁻² M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3′,5′-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3′,5′-AMP in the directional movement in P. polycephalum is discussed.     

Synthesis and biological activity of 17α-alkynylamide derivatives of estradiol

Seven estradiol (E₂) derivatives with an alkynylamide side chain at the 17α position were synthesized starting from ethynylestradiol (EE₂). The main chemical step was the coupling reaction of the acetylide ion of EE₂ with carbon dioxide, glutaric anhydride or bromoalkyl ortho ester. The synthesis of these compounds is fast (3–6 steps according to the compound) and is easily achieved with good yield. Five compounds with different side chain lenghts were evaluated for uterotrophic and antiuterotrophic activity in the CD-1 mouse. None of the tested compounds shows estrogenic activity in this sensitive in vitro system. At low doses (1 and 3 μg), a 14–57% inhibition of E₂-induced uterine growth was observed while no additional inhibition was observed at the 10, 20 and 30 μg doses. In human breast carcinoma cells in culture, all compounds show estrogenic activity at high concentrations while only compound 39 (N-buty,N-methyl-8-[3′,17′β-dihydroxy estra-1′,3′,5′(10′)-trien-17′α-yl]-7-octynamide) possesses antiproliferative or antiestrogenic effects. No significant correlation could be demonstrated between alkynylamide side chain length and estrogenic or antiestrogenic activity. Among the compounds tested, the derivative of EE₂ possessing a five-methylene (CH₂) side chain (compound 39) possesses the best antiestrogenic activity (44 ± 7% in the CD-1 mouse uterus assay at the 3μg dose and 57 ± 4% at 0.1 nM in human ZR-75-1 cancer cells in culture).     

Synthesis and characterization of copper and manganese complexes of monodentate functionalized isocyanide: trimethylsilylmethylisocyanide and p-tolylsulfonylmethylisocyanide

Reaction of excess CNCH₂SiMe₃(L) with CuX₂·nH₂O (X=NO₃⁻, n=3; ClO₄⁻, n=6) in THF gives the Cu^I complexes [CuL₄]NO₃ (1) and [CuL₄]ClO₄ (2). When CuCN is used as starting material, complex 3, Cu(L₃)CN, C₄H₁₀O·3H₂O, is obtained. Immediate reduction occurs with AgNO₃ precipitating metallic Ag. Reactions with MnCl₂·6H₂O and Mn(NO₃)₂·6H₂O in THF produce two new compounds which analyze as MnL₄Cl₂·4H₂O (6) and MnL₂(NO₃)₂·H₂O (7). When excess p-tolylsulfonylmethylisocyanide (L′) is reacted with Cu(NO₃)₂, the mixed-valence Cu^I---Cu^II complex Cu₂L′₆(NO₃)₃ (5) is precipitated, while using CuCN gives the Cu^I dimer Cu₂L′₄(CN)₂ (4). In analogous conditions the manganese complex MnL′₂(NO₃)₂·C₃H₆O·3H₂O (8) is precipitated. All these complexes have been isolated, characterized by IR, NMR for diamagnetic species, magnetic susceptibilities, EPR measurements and electrochemical analyses. Influence of the two substituents is discussed.     

A study of the reactivity and structure of cyclic α,β-unsaturated Fischer-type carbene complexes

Cycloaddition reactions with α,β-unsaturated carbene complexes of the Fischer-type bearing the carbene carbon atom and the double bond incorporated in the same ring are described. Pentacarbonyl(2H-benzopyran-2- ylidene)chromium(0) complexes (2a-c) and pentacarbonyl(4-methoxy-3,3-dimethyl-2-oxacyclopentylidene)- chromium(0) (3) show a rather low reactivity towards 1,3-dipoles and 1,3-dienes. The reactions with diazomethane are regioselective but not chemoselective; compounds 2 and 3 show two sites of attack: the α,β carbon-carbon and the carbon-metal double bond. The crystal and molecular structures of 2a and 3 have been elucidated by single crystal X-ray analysis. Crystals of 2a are monoclinic, space group P2₁/c, a=7.614(3), b=14.033(3), c=12.766(3) Å, β=95.24°, V=1358.3(7) Å Z=4; crystals of 3 are triclinic, space group P , a=6.553(1), b=9.408(1), c=10.620(1) Å α=92.70(1), β=92.30(1), γ=92.12(1)°, V=653.0(1), ų, Z=2. Final agreement indices for 2a and 3 are R=0.034 and 0.033, respectively. Vibrational properties of the Cr(CO)₅ moiety were interpreted by FT-IR and FT-Raman spectroscopy. Electronic spectra and π electron distribution were interpreted by resonance Raman spectroscopy.     

The crystal structures of 4,4′-bipyridinium μ-(4,4′-bipyridine)bis[diaquatetranitratoneodymate(III)]-tris(4,4′-bipyridine) and a second monoclinic form of triaquatrinitratoholmium(III) – bis (4,4′-bipyridine)

The structures of (4-bipyH)₂[(μ-4-bipy)Nd₂(NO₃)₈(H₂O)₄]·3(4-bipy) (4-bipy = 4,4′-bipyridine; P2₁/c, a = 18.723(10), b = 10.720(6), c = 18.027(10) Å, β = 94.43(5)°, Z = 2; R = 0.066 for 4931 (diffractometer data) and of a second monoclinic form of [Ho(NO₃)₃(H₂O)₃]·2(4-bipy) (P2₁/c, a = 15.830(10), b = 21.44(3), c = 15.70(3) Å, β = 100.4(2)°, Z = 8; R = 0.091 for 2335 film data) are reported. In the first compound pairs of Nd atoms are bridged across a crystal inversion centre by a 4-bipy ligand, and 10-coordination is completed by one monodentate NO₃, three bidentate NO₃, and two H₂O ligands, with bond lengths Nd---N 2.70, Nd---OH₂(av.) 2.44, Nd---O(NO₃, av.) 2.56 Å. The second compound has a variant of the previously-reported monoclinic [Y(NO₃)₃(H₂O)₃]·2(4-bipy) structure, with doubling of the unit cell on a but with essentially no change in the geometry and orientation of the nine-coordinate complex. In both compounds the non-coordinated, non-protonated 4-bipy N atoms form hydrogen bonds with ligand H₂O.     

Synthesis of Neu5Ac- and Neu5Gc-α-(2→6′)-lactosamine 3-aminopropyl glycosides

In order to prepare 3-aminopropyl glycosides of Neu5Ac-α-(2→6′)-lactosamine trisaccharide 1, and its N-glycolyl containing analogue Neu5Gc-α-(2→6′)-lactosamine 2, a series of lactosamine acceptors with two, three, and four free OH groups in the galactose residue was studied in glycosylations with a conventional sialyl donor phenyl [methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio- -glycero-α- and β- -galacto-2-nonulopyranosid]onates (3) and a new donor phenyl [methyl 4,7,8,9-tetra-O-acetyl-5-(N-tert-butoxycarbonylacetamido)-3,5-dideoxy-2-thio- -glycero-α- and β- -galacto-2-nonulopyranosid]onates (4), respectively. The lactosamine 4′,6′-diol acceptor was found to be the most efficient in glycosylation with both 3 and 4, while imide-type donor 4 gave slightly higher yields with all acceptors, and isolation of the reaction products was more convenient. In the trisaccharides, obtained by glycosylation with donor 4, the 5-(N-tert-butoxycarbonylacetamido) moiety in the neuraminic acid could be efficiently transformed into the desired N-glycolyl fragment, indicating that such protected oligosaccharide derivatives are valuable precursors of sialo-oligosaccharides containing N-modified analogues of Neu5Ac.     

Enzymatic synthesis of α- -fucosyl-N-acetyllactosamines and 3′-O-α- -fucosyllactose utilizing α- -fucosidases

An α- -fucosidase from porcine liver produced α- -Fuc-(1→2)-β- -Gal-(1→4)- -GlcNAc (2′-O-α- -fucosyl-N-acetyllactosamine, 1) together with its isomers α- -Fuc-(1→3)-β- -Gal-(1→4)- -GlcNAc (2) and α- -Fuc-(1→6)-β- -Gal-(1→4)- -GlcNAc (3) through a transglycosylation reaction from p-nitrophenyl α- -fucopyranoside and β- -Gal-(1→4)- -GlcNAc. The enzyme formed the trisaccharides 1–3 in 13% overall yield based on the donor, and in the ratio of 40:37:23. In contrast, transglycosylation by Alcaligenes sp. α- -fucosidase led to the regioselective synthesis of trisaccharides containing a (1→3)-linked α- -fucosyl residue. When β- -Gal-(1→4)- -GlcNAc and lactose were acceptors, the enzyme formed regioselectively compound 2 and α- -Fuc-(1→3)-β- -Gal-(1→4)- -Glc (3′-O-α- -fucosyllactose, 4), respectively, in 54 and 34% yields, based on the donor.     

Synthesis, and carbon-13 n.m.r. study, of O-α- -rhamnopyranosyl-(1→3)-O-α- -rhamnopyranosyl-(1→2)- -rhamnopyranose and O-α- -rhamnopyranosyl-(1→3)-O-α- -rhamnopyranosyl (1→3)- -rhamnopyranose, constituents of bacterial, cell-wall polysaccharides

O-α- -Rhamnopyranosyl-(1→3)- -rhamnopyranose (19) and O-α- -rhamnopyranosyl-(1→2)- -rhamnopyranose were obtained by reaction of benzyl 2,4- (7) and 3,4-di-O-benzyl-α- -rhamnopyranoside (8) with 2,3,4-tri-O-acetyl-α- -rhamnopyranosyl bromide, followed by deprotection. The per-O-acetyl α-bromide (18) of 19 yielded, by reaction with 8 and 7, the protected derivatives of the title trisaccharides (25 and 23, respectively), from which 25 and 23 were obtained by Zemplén deacetylation and catalytic hydrogenolysis, With benzyl 2,3,4-tri-O-benzyl-β- -galactopyranoside, compound 18 gave an ≈3:2 mixture of benzyl 2,3,4-tri-O-benzyl-6-O-[2,4-di-O-acetyl-3-O-(2,3,4-tri-O-acetyl-α- -rhamnopyranosyl)-α- -rhamnopyranosyl]-β- -galactopyranoside and 4-O-acetyl-3-O-(2,3,4-tri-O-acetyl-α- -rhamnopyranosyl)-β- -rhamnopyranose 1,2-(1,2,3,4-tetra-O-benzyl-β- -galactopyranose-6-yl (orthoacetate). The downfield shift at the α-carbon atom induced by α- -rhamnopyranosylation at HO-2 or -3 of a free α- -rhamnopyranose is 7.4-8.2 p.p.m., ≈1 p.p.m. higher than when the (reducing-end) rhamnose residue is benzyl-protected (6.6-6.9 p.p.m.). α- -Rhamnopyranosylation of HO-6 of gb- -galactopyranose deshields the C-6 atom by 5.7 p.p.m. The 1 2-orthoester ring structure [O₂,C(me)OR] gives characteristic resonances at 24.5 ±0.2 p.p.m. for the methyl, and at 124.0 ±0.5 p.p.m. for the quaternary, carbon atom.     

2′-Azido-2′-deoxy- and 2′-amino-2′-deoxy-β-d-arabino-furanosyl purine nucleosides

A general method for the preparation of 2′-azido-2′-deoxy- and 2′-amino-2′-deoxyarabinofuranosyl-adenine and -guanine nucleosides is described. Selective benzoylation of 3-azido-3-deoxy-1,2-O-isopropylidene-α-d-glucofuranose afforded 3-azido-6-O-benzoyl-3-deoxy-1,2-O-isopropylidene-α-d-glucofuranose (1). Acid hydrolysis of 1, followed by oxidation with sodium metaperiodate and hydrolysis by sodium hydrogencarbonate gave 2-azido-2-deoxy-5-O-benzoyl-d-arabinofuranose (3), which was acetylated to give 1,3-di-O-acetyl-2-azido-5-O-benzoyl-2-deoxy-d-arabinofuranose (4). Compound 4 was converted into the 1-chlorides 5 and 6, which were condensed with silylated derivatives of 6-chloropurine and 2-acetamido-hypoxanthine. The condensation reaction gave α and β anomers of both 7- and 9-substituted purine nucleosides. The structures of the nucleosides were determined by n.m.r. and u.v. spectroscopy, and by correlation of the c.d. spectra of the newly prepared nucleosides with those published for known purine nucleosides.     

1′,2′-Dideacetylboronolide, an α-pyrone from Iboza riparia

The structural elucidation of 1′,2′-dideacetylboronolide, 5,6-dihydro-6-(3′-acetoxy-1′,2′-dihydroxyheptyl)2-pyrone, a new α-pyrone isolated from the leaves of Iboza riparia has been performed. Additionally, three sterols, sitosterol, stigmasterol and campesterol, have been identified in this species.