Synthesis of Ribonucleosidic Dimers with an Amide Linkage from d‑Xylose

An original and efficient stereocontrolled synthesis of ribonucleosidic homo- and heterodimers has been achieved from inexpensive d-xylose. This successful strategy involved the sequential introduction of nucleobases, using two stereocontrolled <i>N</i>-glycosidation reactions, from a common two-furanoside amide-linked scaffold offering the possibility of obtaining any given base sequence. The pertinence of this approach is illustrated through the preparation of the homodimers UU-<b>34</b> and TT-<b>35</b> in 18 steps with an excellent overall yield of more than 10% from d-xylose, while the heterodimer route led to UT-<b>39</b> in 19 steps with around 10% overall yield

Identification of a Foldaxane Kinetic Byproduct during Guest-Induced Single to Double Helix Conversion

An aromatic oligoamide sequence was designed and synthesized to fold in a single helix having a large cavity and to behave as a host for a dumbbell-shaped guest derived from tartaric acid. NMR, molecular modeling, and circular dichroism (CD) evidence demonstrated the rapid formation of this 1:1 host–guest complex and induction of the helix handedness of the host by the guest. This complex was found to be a long-lived kinetic supramolecular byproduct, as it slowly transformed into a 2:2 host–guest complex with two guest molecules bound at the extremities of a double helix formed by the host, as shown by NMR and CD spectroscopy and a solid-state structure. The guest also induced the handedness of the double helical host, but with an opposite bias. The chiroptical properties of the system were thus found to revert with time as the 1:1 complex formed first, followed by the 2:2 complex

1‑Oxo‑1<i>H</i>‑phenalene-2,3-dicarbonitrile Heteroaromatic Scaffold: Revised Structure and Mechanistic Studies

Synthesis of the originally proposed 8-oxo-8<i>H</i>-acenaphtho­[1,2-<i>b</i>]­pyrrol-9-carbonitrile led to a structural revision, and the product has now been identified as unknown compound 1-oxo-1<i>H</i>-phenalene-2,3-dicarbonitrile. The structural assignment was corroborated by detailed NMR studies and unambiguously confirmed by X-ray diffraction. A mechanism is proposed to explain the formation of this original heterocyclic scaffold. In addition, some new chemical transformations involving this compound are presented

1‑Oxo‑1<i>H</i>‑phenalene-2,3-dicarbonitrile Heteroaromatic Scaffold: Revised Structure and Mechanistic Studies

Synthesis of the originally proposed 8-oxo-8<i>H</i>-acenaphtho­[1,2-<i>b</i>]­pyrrol-9-carbonitrile led to a structural revision, and the product has now been identified as unknown compound 1-oxo-1<i>H</i>-phenalene-2,3-dicarbonitrile. The structural assignment was corroborated by detailed NMR studies and unambiguously confirmed by X-ray diffraction. A mechanism is proposed to explain the formation of this original heterocyclic scaffold. In addition, some new chemical transformations involving this compound are presented

Long-Range Effects on the Capture and Release of a Chiral Guest by a Helical Molecular Capsule

Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by ¹H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host–guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend. Three independent observations (direct monitoring of exchange over time, 2D-EXSY NMR, and molecular modeling) concur and show that guest exchange rates tend to first increase upon increasing helix length and then decrease when helix length is increased further. This investigation thus reveals the complex effects of adding monomers in a helically folded sequence on a binding event that occurs at a remote site and sheds light on possible binding and release mechanisms

Reaction of Glyconitriles with Organometallic Reagents: Access to Acyl β‑<i>C</i>‑Glycosides

A new strategy for the synthesis of acyl β-<i>C</i>-glycosides is described. The reactivity of glyconitriles toward organometallic reagents such as organomagnesium or organolithium derivatives was studied, affording acyl β-<i>C</i>-glycosides in moderate to good yields. In this study, glycal formation was efficiently prevented by deprotonating the hydroxyl group in position 2 of the glyconitriles during the process

An Electrochemical Nickel-Catalyzed Arylation of 3‑Amino-6-Chloropyridazines

3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses

3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues <b>8</b> and <b>9</b>, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T_H1 or T_H2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation