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Abstract: The first single-crystal X-ray diffraction study of tetrafluorinated monosaccharide derivatives is presented. Both α- and β-methyl 2,3-dideoxy-2,2,3,3-tetrafluoro-d-galactopyranoside anomers adopt the 4 C 1 conformation. The values for the C1–O1 and C1–O5 bond lengths and the O5–C1–O1–CH3 dihedral angles are in line with what can be expected from the anomeric and exo-anomeric effects. The chair conformations are slightly distorted, presumably due to repulsion between 1,3-diaxial C–O and C–F bonds. The asymmetric unit of both compounds contains up to three independent molecules, which differ in the conformation of the hydroxymethyl group (including in one case a ‘forbidden’gg rotamer). The molecular packing of the β-anomer shows a clear segregation between fluorinated and hydrophilic domains, while for the α-anomer the regions of fluorine segregation are broken by interleafing of OMe groups. There is one close OH⋯F contact, which is likely to arise from the crystal packing. NMR studies show that the two anomers also adopt a 4 C 1 conformation in solution (D2O, CDCl3). [Copyright &y& Elsevier]

Abstract: The C 2-symmetric, butane diacetal (BDA) auxiliary-based dienes 2 and 3 are described, which display moderate to excellent diastereoselectivities in Diels–Alder reactions with a range of dienophiles under thermal and Lewis acid-catalysed conditions. [Copyright &y& Elsevier]

Gemcitabine, 2′-deoxy-2′,2′-difluorocytidine, is currently prescribed against a number of cancers. Here we report a linear synthesis of gemcitabine with a high-yielding direct conversion of 3,5-di- O -benzoyl-2-deoxy-2,2-difluororibose into the corresponding glycosyl urea as the key step, followed by conventional conversion to the cytosine base via the uracil derivative. The process proceeded with modest anomeric selectivity. [ABSTRACT FROM AUTHOR]

The selective synthesis of fluoroalkenoates is reported from a pyrimidinyl fluorosulfone. This sulfone allowed the preparation of Z-fluoroalkenoates with very high stereoselectivity from both aromatic and aliphatic aldehydes. The nature of the heterocycle on the course of the Julia-Kocienski reaction is discussed. [ABSTRACT FROM AUTHOR]

Abstract: An improved large-scale synthesis of 1,2:4,5-dianhydro-3-benzylarabitol and 1,2:4,5-dianhydroarabitol from arabitol is described. [Copyright &y& Elsevier]

A novel procedure for the conversion of primary and secondary alcohols into the corresponding alkyl chlorides, bromides and iodides is described. The transformation is high-yielding in the case of chlorides and bromides, tolerates a range of functional groups, and does not rely on the use of phosphines. [Copyright &y& Elsevier]

iNKT cells recognize CD1d/α-galactosylceramide (α-GalCer) complexes via their invariant TCR receptor and stimulate the immune response. Many α-GalCer analogues have been investigated to interrogate this interaction. Following our previous work related to the modification of the hydrogen bond network between α-GalCer and CD1d, we have now focused our attention on the synthesis of 3-deoxy-3,3-difluoro- and 3,4-dideoxy-3,3,4,4-tetrafluoro-α-GalCer analogues, and studied their ability to stimulate human i NKT cells. In each case, deoxygenation at the indicated positions was accompanied by difluoro introduction in order to evaluate the resulting electronic effect on the stability of the ternary CD1d/Galcer/TCR complex which has been rationalized by modeling study. With deoxy-difluorination at the 3-position, the two epimeric 4-OH analogues were investigated to establish their capacity to compensate for the lack of the hydrogen bond donating group at the 3-position. The 3,4-dideoxytetrafluoro analogue was of interest to highlight the amide NH -bond hydrogen bond properties. Image 1 • H-bonding of the 3-OH and the amide NH groups on the iNKT stimulation process. • Synthesis of 3,4-dideoxy-3-fluoro- and 3,4-dideoxy-3,3-difluoro-KRN7000 analogues. • Co-participation of 4-OH on key 3-OH contribution in KRN7000 immune stimulation. • Potency of the tetrafluorinated analogue to highlight contribution of the NH group. [ABSTRACT FROM AUTHOR]

Abstract The interplay of the relative configuration of diastereomeric vicinal difluoride groups on the conformational properties of polyesters has been investigated and compared to their non-fluorinated and per-fluorinated counterparts. The incorporation of syn and meso vicinal difluoride units in the polymer backbone was expected to influence the rigidity and stacking behaviour of the polymers in a significant way, and therefore to result in different thermal properties, such as melting point and melting enthalpy. Both syn and meso -2,3-difluoro butanediol have been reacted with the diester dimethyl succinate, leading to the formation of polyesters that have been characterized with 1H, 13C and 19F NMR. The polyesters showed molar masses up to 20 kg/mol (SEC). Surprisingly, the syn and meso -polymers displayed identical crystallization and melting behaviour. In contrast, differences were observed in the crystallization kinetics and melting points of syn and meso oligomers. Relying on time-resolved synchrotron SAXS and WAXD experiments, the complex multiple melting behaviour of these oligomers was explained in terms of crystal size and surface effects. The slower crystallization kinetics for the meso oligomers was tentatively associated with a stronger tendency to adopt gauche configurations. Apparently, such effects no longer affect the crystallization kinetics when larger polymers crystallize. It was also found that the syn and meso -polymers have identical equilibrium melting points and melting enthalpies notwithstanding molecular and crystallographic differences. Graphical abstract Image 1 Highlights • Formation of polyesters from s yn and meso -2,3-difluoro butanediol and a diester. • Effect of the configuration of diastereomeric difluorides on the conformation. • Syn and meso -polymers displayed identical crystallization and melting behaviour. • Syn and meso - oligomers displayed differences in crystallization and melting point. • Slower crystallization kinetics for the meso oligomers due to gauche configurations. [ABSTRACT FROM AUTHOR]

The regioselective protection of both methyl galactopyranoside anomers at the 2 and 3-positions as the butane diacetal (BDA) is well known. Here we describe the formation of an unexpected byproduct, which mainly occurs when α-methyl galactopyranoside is reacted with 2,3-butanedione under BF 3 •OEt 2 catalysis. The structure of the byproduct, which did not arise from anomerisation to the β-anomer or from BDA formation at the galactopyranoside 3,4-positions, was elucidated by NMR and X-ray crystallographic analysis, and proved to be the expected BDA protected galactopyranoside, but in which the stereochemistry of both its BDA acetal centres are inverted. Interestingly, the conformation of the resulting six-membered BDA ring was distorted to a skew boat conformation in order to maintain anomeric stabilisation. [ABSTRACT FROM AUTHOR]

A three-step synthesis of enantiomerically enriched 1,1,1-trifluoro-2-propanamine based on the use of a chiral sulfinamide auxiliary is described. The reduction of the geometrically pure Z -sulfinimine (NOE, HOE) with NaBH 4 or l -Selectride leads to the corresponding ( R )- or ( S )-configured amine derivatives (X-ray crystallographic analysis) with 92–96% de . The typical models to explain the stereoselection for these reducing agents fail to rationalize the obtained stereoselectivities, and an in situ imine isomerization is proposed to occur. The direct use of the hydrochloric acid salt (with excess Et 3 N) of this poorly nucleophilic amine for epoxide opening reactions is not possible due to the higher nucleophilicity of chloride. Hence, a novel triflate salt is introduced, synthesized through ready sulfinamide hydrolysis with trimethylsilyl triflate, which can be used directly, without the need of isolating the pure amine beforehand. [ABSTRACT FROM AUTHOR]

Highlights: [•] Gemcitabine is a 2′,2′-difluorinated nucleoside. [•] The 2-deoxy-2,2-difluorinated ribose has been synthesised by a variety of approaches. [•] The sugar fluorination required modified nucleobase introduction. [•] Extensive efforts to achieve diastereomerically pure intermediates are described. [ABSTRACT FROM AUTHOR]

Abstract: Analogues of potent 5-HT4R antagonists possessing a fluorinated N-alkyl chain have been synthesized in order to investigate the effect of the resulting change in basicity and lipophilicity on the affinity and selectivity profile. We demonstrate that for this series, the affinity is decreased with decreased basicity of the piperidine’s nitrogen atom. In contrast, the resulting increase in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3-Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind to the 5-HT4R while maintaining their pharmacological profile and selectivity toward other 5-HT receptors. [Copyright &y& Elsevier]

Abstract: Enantiopure carbafuranose derivatives were synthesised via a linchpin carbacyclisation process starting from 1,4-bisepoxides. Both 2-deoxy and 2-deoxy-6-hydroxycarbafuranose derivatives were obtained, which were converted to suitably protected precursors for carbanucleoside synthesis. [Copyright &y& Elsevier]

Tris-1,1,1-(hydroxymethyl)ethane 1 was converted to a series of mono- and disubstituted derivatives. An indirect protocol for the differentiation of the alcohol groups was employed for the synthesis of partially and fully differentiated 1 containing a protected aldehyde unit. Complete differentiation of the alcohol groups was also achieved using a direct strategy (two steps from 1). The first synthesis of 1,3-dialdehydes derived from 1 is reported in two steps. [Copyright &y& Elsevier]

Image 1 • Glycosyl 1-phosphate chemical synthesis. • Anomeric phosphorylation of acetylated precursors. • Evaluation of glycosylation methodology to access native and modified glycosyl 1-phosphates. [ABSTRACT FROM AUTHOR]