Highly Stereoselective β‐Mannopyranosylation via the 1‐α‐Glycosyloxy‐isochromenylium‐4‐gold(I) Intermediates

While the gold(I)‐catalyzed glycosylation reaction with 4,6‐O‐benzylidene tethered mannosyl ortho‐alkynylbenzoates as donors falls squarely into the category of the Crich‐type β‐selective mannosylation when Ph₃PAuOTf is used as the catalyst, in that the mannosyl α‐triflates are invoked, replacement of the ^?OTf in the gold(I) complex with less nucleophilic counter anions (i.e., ^?NTf₂, ^?SbF₆, ^?BF₄, and ^?BAr₄^F) leads to complete loss of β‐selectivity with the mannosyl ortho‐alkynylbenzoate β‐donors. Nevertheless, with the α‐donors, the mannosylation reactions under the catalysis of Ph₃PAuBAr₄^F (BAr₄^F=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate) are especially highly β‐selective and accommodate a broad scope of substrates; these include glycosylation with mannosyl donors installed with a bulky TBS group at O3, donors bearing 4,6‐di‐O‐benzoyl groups, and acceptors known as sterically unmatched or hindered. For the ortho‐alkynylbenzoate β‐donors, an anomerization and glycosylation sequence can also ensure the highly β‐selective mannosylation. The 1‐α‐mannosyloxy‐isochromenylium‐4‐gold(I) complex ( Cα ), readily generated upon activation of the α‐mannosyl ortho‐alkynylbenzoate ( 1 α ) with Ph₃PAuBAr₄^F at ?35 °C, was well characterized by NMR spectroscopy; the occurrence of this species accounts for the high β‐selectivity in the present mannosylation.     

σ‐Alkylpalladium Intermediates in Intramolecular Heck Reactions:Isolation and Catalytic Activity

The isolation of σ‐alkylpalladium Heck intermediates, possible when β‐hydride elimination is inhibited, is a rather rare event. Performing intramolecular Heck reactions on N‐allyl‐2‐halobenzylamines in the presence of [Pd(PPh₃)₄], we isolated and characterized a series of stable bridged palladacycles containing an iodine or bromine atom on the palladium atom. Indolyl substrates were also tested for isolation of the corresponding complexes. X‐ray crystallographic analysis of one of the indolyl derivatives revealed the presence of a five‐membered palladacycle with the metal center bearing a PPh₃ ligand and an iodine atom in a cis position with respect to the nitrogen atom. The stability of the σ‐alkylpalladium complexes is probably a consequence of the strong constraint resulting from the bridged junction that hampers the cisoid conformation essential for β‐hydride elimination. Subsequently, the thus obtained bridged five‐membered palladacycles were proven to be effective precatalysts in Heck reactions as well as in cross‐coupling processes such as Suzuki and Stille reactions.     

1‐(β‐d‐Erythrofuranos­yl)cytidine (β‐erythrocytidine)

1‐(β‐d ‐Erythrofuranosyl)cytidine, C₈H₁₁N₃O₄, (I), a derivative of β‐cytidine, (II), lacks an exocyclic hydroxy­methyl (–CH₂OH) substituent at C4′ and crystallizes in a global conformation different from that observed for (II). In (I), the β‐d ‐erythrofuranosyl ring assumes an E₃ conformation (C3′‐exo; S, i.e. south), and the N‐glycoside bond conformation is syn. In contrast, (II) contains a β‐d ‐ribofuranosyl ring in a ³T₂ conformation (N, i.e. north) and an anti‐N‐glycoside linkage. These crystallographic properties mimic those found in aqueous solution by NMR with respect to furan­ose conformation. Removal of the –CH₂OH group thus affects the global conformation of the aldofuranosyl ring. These results provide further support for S/syn–anti and N/anti correlations in pyrimidine nucleosides. The crystal structure of (I) was determined at 200 K.     

Poly[[μ2‐1,3‐bis(pyridin‐4‐yl)propane](μ3‐1,4‐phenylenediacetato)cadmium]

Solvothermal reaction between Cd(NO₃)₂, 1,4‐phenylenediacetate (1,4‐PDA) and 1,3‐bis(pyridin‐4‐yl)propane (bpp) afforded the title complex, [Cd(C₁₀H₈O₄)(C₁₃H₁₄N₂)]_n. Adjacent carboxylate‐bridged Cd^II ions are related by an inversion centre. The 1,4‐PDA ligands adopt a cis conformation and connect the Cd^II ions to form a one‐dimensional chain extending along the c axis. These chains are in turn linked into a two‐dimensional network through bpp bridges. The bpp ligands adopt an anti–gauche conformation. From a topological point of view, each bpp ligand and each pair of 1,4‐PDA ligands can be considered as linkers, while the dinuclear Cd^II unit can be regarded as a 6‐connecting node. Thus, the structure can be simplified to a two‐dimensional 6‐connected network.     

12‐ to 22‐Membered Bridged β‐Lactams as Potential Penicillin‐Binding Protein Inhibitors

As potential inhibitors of penicillin‐binding proteins (PBPs), we focused our research on the synthesis of non‐traditional 1,3‐bridged β‐lactams embedded into macrocycles. We synthesized 12‐ to 22‐membered bicyclic β‐lactams by the ring‐closing metathesis (RCM) of bis‐ω‐alkenyl‐3(S)‐aminoazetidinone precursors. The reactivity of 1,3‐bridged β‐lactams was estimated by the determination of the energy barrier of a concerted nucleophilic attack and lactam ring‐opening process by using ab initio calculations. The results predicted that 16‐membered cycles should be more reactive. Biochemical evaluations against R39 DD‐peptidase and two resistant PBPs, namely, PBP2a and PBP5, revealed the inhibition effect of compound 4d , which featured a 16‐membered bridge and the N‐tert‐butyloxycarbonyl chain at the C3 position of the β‐lactam ring. Surprisingly, the corresponding bicycle, 12d , with the PhOCH₂CO side chain at C3 was inactive. Reaction models of the R39 active site gave a new insight into the geometric requirements of the conformation of potential ligands and their steric hindrance; this could help in the design of new compounds.     

X‐ray investigations of bicyclic α‐methyl­ene‐δ‐valerolactones. II. (4aS,8aS)‐4a‐Methyl‐3‐methyl­eneper­hydro­chromen‐2‐one

The title compound, C₁₁H₁₆O₂, adopts a semifolded conformation with the δ‐lactone and cyclo­hexane rings almost perpendicular to one another. The β‐methyl substituent occupies an axial position with respect to the cyclo­hexane ring. The δ‐lactone moiety adopts a slightly distorted half‐chair arrangement, while the cyclo­hexane ring exists in an almost ideal chair conformation.     

2,6‐Bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine and its octahedral copper complex

In the tridentate ligand 2,6‐bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine, C₂₃H₁₉N₇, both sets of triazole N atoms are anti with respect to the pyridine N atom, while in the copper complex aqua[2,6‐bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine](pyridine)(tetrafluoroborato)copper(II) tetrafluoroborate, [Cu(BF₄)(C₅H₅N)(C₂₃H₁₉N₇)(H₂O)]BF₄, the triazole N atoms are in the syn–syn conformation. The coordination of the Cu^II atom is distorted octahedral. The ligand structure is stabilized through intermolecular C—H...N interactions, while the crystal structure of the Cu complex is stabilized through water‐ and BF₄‐mediated hydrogen bonds. Photoluminiscence studies of the ligand and complex show that the ligand is fluorescent due to triazole–pyridine conjugation, but that the fluorescence is quenched on complexation.     

Synthesis and Structures of β‐Diketoiminate Complexes of Magnesium

The reaction of the β‐diketoiminate lithium complex (dipp)NacNacLi · OEt₂ ((dipp)NacNac = 2‐((2,6‐diisopropylphenyl)amino)‐4‐((2,6‐diisopropylphenyl)imino)‐pent‐2‐enyl) with iPrMgCl and MgI₂ yield the corresponding (dipp)NacNacMgiPr · OEt₂ ( 1 ) and (dipp)NacNacMgI · OEt₂ ( 2 ). The reaction of 2 with NaBH₄ in diethylether gives (dipp)NacNacMg(μ‐H)₃BH · OEt₂ ( 3 ). The core element of compounds 1 – 3 is a six‐membered ring formed by N(1)–C(1)–C(2)–C(3)–N(2) and magnesium. The structures of 1 and 2 show the β‐diketoiminate backbone in a boat‐conformation with the tetrahedrally coordinated metal center at the prow and the opposing carbon atom at the stern. The magnesium atom in 3 is octahedrally coordinated and out of the β‐diketoiminate plane.     

3‐Deoxy‐β‐d‐ribo‐hexopyranose (3‐deoxy‐β‐d‐glucopyranose)

The β‐pyranose form, (III), of 3‐deoxy‐d ‐ribo‐hexose (3‐deoxy‐d ‐glucose), C₆H₁₂O₅, crystallizes from water at 298 K in a slightly distorted ⁴C₁ chair conformation. Structural analyses of (III), β‐d ‐glucopyranose, (IV), and 2‐deoxy‐β‐d ‐arabino‐hexopyranose (2‐deoxy‐β‐d ‐glucopyranose), (V), show significantly different C—O bond torsions involving the anomeric carbon, with the H—C—O—H torsion angle approaching an eclipsed conformation in (III) (−10.9°) compared with 32.8 and 32.5° in (IV) and (V), respectively. Ring carbon deoxygenation significantly affects the endo‐ and exocyclic C—C and C—O bond lengths throughout the pyranose ring, with longer bonds generally observed in the monodeoxygenated species (III) and (V) compared with (IV). These structural changes are attributed to differences in exocyclic C—O bond conformations and/or hydrogen‐bonding patterns superimposed on the direct (intrinsic) effect of monodeoxygenation. The exocyclic hydroxymethyl conformation in (III) (gt) differs from that observed in (IV) and (V) (gg).     

The unusual ability of α‐angelicalactone to form adducts: A kinetic approach

Since α‐angelicalactone (AAL) substantially inhibits the formation of tumors, here its chemical reactivity was compared with that of carcinogenic lactones. Investigation of the electrophilic potential of AAL was carried out by studying the capacity of this lactone to form adducts with NBP, 4‐(p‐nitrobenzyl)pyridine, a substrate with nucleophilic characteristics similar to DNA bases. The formation of the AAL–NBP adduct occurs about 900,000‐fold faster than with β‐propiolactone, the most effective carcinogenic lactone (ΔG^#₃₅ = 52 and 87 kJ mol^?1, respectively). A stopped‐flow technique was required for this reaction to be monitored. It was concluded that the formation of AAL–NBP adducts takes place through an entropy‐strain‐catalyzed mechanism caused by early lactone ring cleavage. The kinetic results are consistent with the AAL potential as a chemoprotective agent. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 591–594, 2007     

Methyl β‐allolactoside [methyl β‐d‐galactopyranosyl‐(1→6)‐β‐d‐glucopyranoside] monohydrate

Methyl β‐allolactoside [methyl β‐d ‐galactopyranosyl‐(1→6)‐β‐d ‐glucopyranoside], (II), was crystallized from water as a monohydrate, C₁₃H₂₄O₁₁·H₂O. The βGalp and βGlcp residues in (II) assume distorted ⁴C₁ chair conformations, with the former more distorted than the latter. Linkage conformation is characterized by ϕ′ (C2_Gal—C1_Gal—O1_Gal—C6_Glc), ψ′ (C1_Gal—O1_Gal—C6_Glc—C5_Glc) and ω (C4_Glc—C5_Glc—C6_Glc—O1_Gal) torsion angles of 172.9 (2), −117.9 (3) and −176.2 (2)°, respectively. The ψ′ and ω values differ significantly from those found in the crystal structure of β‐gentiobiose, (III) [Rohrer et al. (1980). Acta Cryst. B 36 , 650–654]. Structural comparisons of (II) with related disaccharides bound to a mutant β‐galactosidase reveal significant differences in hydroxymethyl conformation and in the degree of ring distortion of the βGlcp residue. Structural comparisons of (II) with a DFT‐optimized structure, (II_C), suggest a link between hydrogen bonding, pyranosyl ring deformation and linkage conformation.     

Design of two series of 1:1 cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine and carboxylic acids

Two series of a total of ten cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine with various carboxylic acids have been prepared and characterized by single‐crystal X‐ray diffraction. The pyrimidine unit used for the cocrystals offers two ring N atoms (positions N1 and N3) as proton‐accepting sites. Depending upon the site of protonation, two types of cations are possible [Rajam et al. (2017). Acta Cryst. C 73 , 862–868]. In a parallel arrangement, two series of cocrystals are possible depending upon the hydrogen bonding of the carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐bromothiophene‐2‐carboxylic acid (1/1), 1 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐chlorothiophene‐2‐carboxylic acid (1/1), 2 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2,4‐dichlorobenzoic acid (1/1), 3 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐aminobenzoic acid (1/1), 4 , the carboxyl hydroxy group (–OH) is hydrogen bonded to position N1 (O—H…N1) of the corresponding pyrimidine unit (single point supramolecular synthon). The inversion‐related stacked pyrimidines are doubly bridged by the carboxyl groups via N—H…O and O—H…N hydrogen bonds to form a large cage‐like tetrameric unit with an R₄²(20) graph‐set ring motif. These tetrameric units are further connected via base pairing through a pair of N—H…N hydrogen bonds, generating R₂²(8) motifs (supramolecular homosynthon). In the other series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐methylthiophene‐2‐carboxylic acid (1/1), 5 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–benzoic acid (1/1), 6 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐methylbenzoic acid (1/1), 7 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐methylbenzoic acid (1/1), 8 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐methylbenzoic acid (1/1), 9 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐aminobenzoic acid (1/1), 10 , the carboxyl group interacts with position N3 and the adjacent 4‐amino group of the corresponding pyrimidine ring via O—H…N and N—H…O hydrogen bonds to generate the robust R₂²(8) supramolecular heterosynthon. These heterosynthons are further connected by N—H…N hydrogen‐bond interactions in a linear fashion to form a chain‐like arrangement. In cocrystal 1 , a Br…Br halogen bond is present, in cocrystals 2 and 3 , Cl…Cl halogen bonds are present, and in cocrystals 5 , 6 and 7 , Cl…O halogen bonds are present. In all of the ten cocrystals, π–π stacking interactions are observed.     

Efficient asymmetric addition of diethylzinc to aldehydes using C2‐novel chiral pyridine β‐amino alcohols as chiral ligands

A series of novel C₂‐symmetric chiral pyridine β‐amino alcohol ligands have been synthesized from 2,6‐pyridine dicarboxaldehyde, m‐phthalaldehyde and chiral β‐amino alcohols through a two‐step reaction. All their structures were characterized by ¹H NMR, ¹³C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)‐2,2′‐((pyridine‐2,6‐diylbis(methylene))bisazanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)‐2,2′‐((1,3‐phenylenebis(methylene))bis(azanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

1‐(β‐d‐Erythrofuranosyl)adenosine

The title compound, also known as β‐erythroadenosine, C₉H₁₁N₅O₃, (I), a derivative of β‐adenosine, (II), that lacks the C5′ exocyclic hydroxymethyl (–CH₂OH) substituent, crystallizes from hot ethanol with two independent molecules having different conformations, denoted (IA) and (IB). In (IA), the furanose conformation is ^OT₁–E₁ (C1′‐exo, east), with pseudorotational parameters P and τ_m of 114.4 and 42°, respectively. In contrast, the P and τ_m values are 170.1 and 46°, respectively, in (IB), consistent with a ²E–²T₃ (C2′‐endo, south) conformation. The N‐glycoside conformation is syn (+sc) in (IA) and anti (−ac) in (IB). The crystal structure, determined to a resolution of 2.0 Å, of a cocrystal of (I) bound to the enzyme 5′‐fluorodeoxyadenosine synthase from Streptomyces cattleya shows the furanose ring in a near‐ideal ^OE (east) conformation (P = 90° and τ_m = 42°) and the base in an anti (−ac) conformation.     

PMLABe Diol Synthesized by Ring‐Opening Polymerization of Racemic Benzyl β‐Malolactonate Initiated by Rare‐Earth Trisborohydride Complexes: An Experimental and DFT Study

Polymer diols are a class of polymeric building blocks of high interest for the synthesis of complex macromolecular edifices. Rare‐earth borohydride complexes are known as efficient initiators for the ring‐opening polymerization (ROP) of cyclic esters, directly affording α,ω‐dihydroxy‐telechelic polyesters. Here, were report the direct synthesis of poly(benzyl β‐malolactonate) (PMLABe) diols, from the ROP of racemic (benzyl β‐malolactonate) (rac‐MLABe), a valuable and renewable monomer, initiated by the homoleptic [Ln(BH₄)₃(thf)₃] (Ln=La, Nd, and Sm) complexes. These initiators enabled the controlled ROP of this β‐lactone, affording well‐defined syndiotactic‐enriched (P_r≈0.83) PMLABes (M_n up to 21 300 g mol^?1, Ð_M≈1.5) as evidenced by size exclusion chromatography, ¹H and ¹³C NMR spectroscopy, and MALDI‐ToF mass spectrometry analyses. The first and second insertions of rac‐MLABe, as assessed by DFT calculations, revealed more favorable stationary front‐side than migratory back‐side insertions, the thermodynamically and kinetically competitive ROP on two distinct arms with that on a one arm‐only, and the thermodynamically slightly favored formation of syndiotactic‐enriched PMLABes.     

2,6‐Dimethoxy‐7,9‐dimethylpurinium iodide hemihydrate

In the title compound, C₉H₁₃N₄O₂⁺·I⁻·0.5H₂O, the non‐H atoms of the ionic components lie on a mirror plane in Cmca, with the O atom of the partial water molecule lying on a twofold rotation axis. Whereas one of the methoxy methyl groups is directed away from the adjacent N‐methyl group, the other methoxy methyl group is directed towards its adjacent N‐methyl group. The conformation of the methoxy methyl groups provides an explanation for the outcomes of intramolecular thermal rearrangements of 2,6‐dialkoxy‐7,9‐dimethylpurinium salts.     

Crystallographic report: Coordination polymers containing Cd(NO3)2 and Cd(H2O)22+ units bridged by btp ligands (btp = 2,6‐bis(N′‐1,2,4‐triazolyl)pyridine)

There are two kinds of coordination polymers in the title compound: one contains Cd(NO₃)₂ units bridged by 2,6‐bis(N′‐1,2,4‐triazolyl)pyridine (btp) ligands and the other contains Cd(H₂O)₂²⁺ bridged by btp ligands. The two coordination polymers are connected through hydrogen bonds. Copyright © 2004 John Wiley & Sons, Ltd.     

(4R,4aR,6S,7S,7aS)‐6‐Hydro­xy‐7‐hy­droxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate from Valeriana laxiflora

The structure of an iridolactone isolated from Valeriana laxiflora was established as (4R,4aR,6S,7S,7aS)‐6‐hydroxy‐7‐hydroxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate, C₁₀H₁₆O₄·CHCl₃. The two rings are cis‐fused. The δ‐lactone ring adopts a slightly twisted half‐chair conformation with approximate planarity of the lactone group and the cyclo­pentane ring adopts an envelope conformation. The hydroxy group, the hydroxymethyl group and the methyl group all have β orientations. The absolute configuration was determined using anomalous dispersion data enhanced by the adventitious inclusion of a chloro­form solvent mol­ecule. Hydro­gen bonding, crystal packing and ring conformations are discussed in detail.     

ss‐NMR and single‐crystal X‐ray diffraction in the elucidation of a new polymorph of bischalcone (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one

We report a new polymorph of (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one, C₁₇H₁₂F₂O. Contrary to the precedent literature polymorph with Z′ = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so‐called anti or syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half‐occupied and overlapping molecules presenting both anti and syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C—H…O contacts involving the carbonyl and anti‐oriented β‐C—H groups, which is reflected in three ¹³C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.     

N‐(tert‐Butoxycarbonyl)‐O‐allyl‐l‐seryl‐α‐aminoisobutyryl‐l‐valine methyl ester: a protected tripeptide with an allylated serine residue

The title compound [systematic name (6S,12S)‐methyl 6‐(allyloxymethyl)‐12‐isopropyl‐2,2,9,9‐tetramethyl‐4,7,10‐trioxo‐3‐oxa‐5,8,11‐triazatridecan‐13‐oate], C₂₁H₃₇N₃O₇, containing the little studied O‐allyl‐l ‐serine residue [Ser(All)], crystallizes in the monoclinic space group C2 with one molecule in the asymmetric unit. The compound is an analogue of the Ser140‐Val142 segment of the water channel aquaporin‐4 (AQP4). It forms a distorted type‐II β‐turn with a P_II–3_10L–P_II backbone conformation (P_II is polyproline II). The overall backbone conformation is markedly different from that of the CO(Pro139)–Val142 stretch of rat AQP4, but is quite similar to the corresponding segment of human AQP4, despite significant differences at the level of the individual residues. The side chain of the Ser(All) residue adopts a gauche conformation relative to the backbone CO—C^α and C^α—N bonds. The H atoms of the two CH₂ groups in the Ser(All) side chain are almost eclipsed. The crystal packing of the title compound is divided into one‐molecule‐thick layers, each layer having a hydrophilic core and distinct hydrophobic interfaces on either side.