Graeme J. Gainsford

A β-Fluoroamine Inhibitor of Purine Nucleoside Phosphorylase

The potent immucillin purine nucleoside phosphorylase (PNP ) inhibitors F-DADMe-ImmH [(3S,4S)-3], and [(3R,4R)-3] are synthesized in seven steps. Cycloaddition to a fluoroalkene and an enzymic resolution are the key features of the construction of the fluoropyrrolidines 11, from which the immucillins are assembled by use of a three-component Mannich reaction. Slow-onset binding constants (Ki(*)) for [(3S,4S)-3] and [(3R,4R)-3] with human PNP are 0.032 and 1.82 nM, respectively. F-DADMe-ImmH [(3S,4S)-3] exhibits oral availability in mice at doses as low as 0.2 mg/kg.

Total synthesis of LewisX using a late-stage crystalline intermediate

Herein, we report on a highly efficient synthesis of a crystalline protected Lewis(X) trisaccharide that was converted to Lewis(X) following global deprotection. The trisaccharide was prepared in a highly convergent synthesis (seven steps, longest linear sequence) and in a 38% overall yield using a strategy that involved the regioselective glycosylation of a GlcNAc acceptor with a galactose thioglycoside donor, followed by fucosylation of the remaining free GlcNAc hydroxyl as key steps. The core trisaccharide also has the potential to be converted to other members of the Type-2 Lewis family of antigens due to the orthogonal nature of the protecting groups employed.

N-(2-Acetamido-2-de­oxy-β-d-gluco­pyranos­yl)-N-(3-azido­prop­yl)-O-methyl­hydroxyl­amine

The structure determination of an oxyamine glycoside confirmed that it was obtained in the ring-closed β-pyranose configuration with a 4 C 1 conformation. The molecules are bound by O—H⋯O(OH) hydrogen bonds, notably in a zigzag C(2) chain along the short b (screw) axis, supplemented with an (12) O—H⋯O(carbonyl) link along the a axis and other C(2) links.

2-{2-[5-(4-Cyano-5-di-cyano-methyl-idene-2,2-dimethyl-2,5-di-hydro-furan-3-yl)penta-2,4-dienyl-idene]-3,3-dimethyl-2,3-di-hydro-1H-indol-1-yl}ethyl 3,5-bis-(benz-yloxy)benzoate.

In the title molecule, C48H42N4O5, a potential non-linear optical compound, the furan ring [r.m.s. deviation = 0.010 (1) Å] and the indolylidene ring system [r.m.s. deviation = 0.013 (2) Å] are inclined to one another by 18.52 (6)°. This is similar to the arrangement [16.51 (18)°] found for the N-hydroxyethyl adduct of the title compound [Bhuiyan et al. (2011 ▶). Mol. Cryst. Liq. Cryst. 548, 1–12]. Replacing the hydroxyethyl group with 3,5-dibenzyloxybenzoate has not resulted in a non-centrosymmetric lattice arrangement or significant changes to the basic molecular structure. In the crystal, molecules are linked via pairs of C—H⋯N hydrogen bonds, forming inversion dimers with an R 2 2(20) ring motif. The dimers are linked via C—H⋯O hydrogen bonds, forming C(17) chains along [010]. The chains are linked by further C—H⋯N hydrogen bonds, forming layers parallel to (001) and enclosing R 2 2(44) ring motifs. There are also C—H⋯π interactions present, stabilizing the interlayer orientation of the pendant bis(benzyloxy)benzoyloxy group.

Acet-oxy-γ-valerolactone.

Levulinyl cellulose esters have been produced as an effective renewable binder for architectural coatings. The title compound, C7H10O4 (systematic name: 2-methyl-5-oxotetrahydrofuran-2-yl acetate), assigned as the esterifying species, was isolated and crystallized to confirm the structure. In the crystal, the molecules pack in layers parallel to (102) utilizing weak C—H⋯O interactions.

2-(3-Cyano-4-{3-[1-(2-hy­droxy­eth­yl)-3,3-dimethyl-1,3-di­hydro­indol-2-yl­idene]prop-2-en­yl}-5,5-dimethyl-5H-furan-2-yl­idene)malono­nitrile

The title compound, C25H24N4O2, adopts a cisoid configuration and has twofold orientational disorder of the 2-hydroxyethyl group. The molecule is twisted from planarity so that the dihedral angle between the terminating indol-2-ylidene and the furan-2-ylidene moiety mean planes is 12.75 (7)°. Conformational disorder occurs at the indol-2-ylidene N atom, which results in two orientations for the hydroxyethyl group [occupancy ratio = 0.896 (2):0.104 (2)], and the hydroxy O atom of the 2-hydroxyethyl group is located over three sites [occupancy ratio = 0.548 (2):0.348 (2):0.104 (2)]. An intramolecular C—H⋯O hydrogen bond involving the lowest occupancy hydroxy O atom is observed. In the crystal, the molecules pack in parallel dimeric sheets about centres of symmetry, utilizing O—H⋯N(cyano), C—H⋯N(cyano) and O—H⋯O hydrogen bonds, in two sets parallel to (02-1) and (021) planes.

1-(2,3-Di­hydroxy­prop­yl)-4-{2-[4-(di­methyl­amino)­phen­yl]vin­yl}pyridinium chloride

The title compound, C18H23N2O2 +·Cl−, crystallizes with two independent cations and anions per cell. Each cation has twofold rotational disorder about the linking vinyl groups but with unequal occupancies [0.963 (5):0.037 (5) and 0.860 (8):0.140 (8)]. The two independent cations are close to being related by an inversion centre but the data does not support the expected centrosymmetric space-group assignment. The conclusion is that the differing rotational disorder has lead to an overall non-centrosymmetric lattice. In the crystal, the molecules pack in layers parallel to (133) and (-13-3), chain-linked with motif C 1 2(7) by the dihydroxypropyl O–H⋯Cl⋯H–O hydrogen bonds. Other lattice binding is provided by O—H⋯Cl, C—H⋯Cl and C—H⋯N interactions.

2-(3-Cyano-4-methyl-5,5-diphenyl-5H-furan-2-yl-idene)malono-nitrile.

The title compound, C21H13N3O, crystallizes with two independent molecules with similar conformations per asymmetric unit. The dihydrofuran rings are essentially planar with maximum deviations of 0.017 (1) and 0.006 (1) Å for the O atoms. The dihedral angles between the dihydrofuran ring and the attached phenyl rings are 79.90 (6) and 82.07 (6)° in one molecule and 79.36 (6) and 72.26 (6)° in the other. In the crystal, the molecules are linked by weak C—H⋯π and C—H⋯N interactions similar to those in other closely related crystals. The replacement of appended methyl by phenyl groups has not significantly affected the dihydrofuran ring structure or the crystal packing interactions.

1-(4-{[(1,3,3-Tri­methyl­indolin-2-yl­idene)meth­yl]diazen­yl}phen­yl)ethanone

The title compound, C20H21N3O, has crystallographic mirror symmetry with all non-H atoms apart from the methyl C atom of the CMe2 group lying on the mirror plane. Molecules are linked into planar sheets parallel to (010) by phenyl–azo C—H⋯N and phenyl–ethanone C—H⋯O interactions. Methyl C—H⋯π interactions provide crosslinking between the planes.

4-Methyl-5-(4-nitro-benzyl-idene)-2-oxo-2,5-di-hydro-1H-pyrrole-3-carbo-nitrile.

Molecules of the potential non-linear optical title compound, C13H9N3O3, form dimeric stacks of molecules along the a axis cross-linked around inversion centers by N—H⋯O hydrogen bonds and weak (phenyl)C—H⋯O intermolecular interactions, forming a ‘collaboration’ of R 2 2(8) and R 2 2(16) ring motifs. The molecules are then further linked by weak C—H⋯O and C—H⋯N interactions into sheets parallel to (121).