On the Origin of Regioselectivity in Palladium-Catalyzed Oxidation of Glucosides

The palladium-catalyzed oxidation of glucopyranosides has been investigated using relativistic density functional theory (DFT) at ZORA-BLYP−D3(BJ)/TZ2P. The complete Gibbs free energy profiles for the oxidation of secondary hydroxy groups at C2, C3, and C4 were computed for methyl β-glucoside and methyl carba-β-glucoside. Both computations and oxidation experiments on carba-glucosides demonstrate the crucial role of the ring oxygen in the C3 regioselectivity observed during the oxidation of glucosides. Analysis of the model systems for oxidized methyl β-glucoside shows that the C3 oxidation product is intrinsically favored in the presence of the ring oxygen. Subsequent energy decomposition analysis (EDA) and Hirschfeld charge analysis reveal the role of the ring oxygen: it positively polarizes C1/C5 by inductive effects and disfavors any subsequent buildup of positive charge at neighboring carbon atoms, rendering C3 the most favored site for the β-hydride elimination

Novel Methods towards Rare Sugars Based on Site-Selective Chemistry

Sugars play important roles in the functions of our bodies. Besides common sugars like glucose and lactose, other rare sugars are found in bacteria and other organisms. These rare sugars can have important biological activities, such as anti-cancer, anti-bacterial and anti-viral. Interestingly, these rare sugars can be extremely similar to the common sugars found in mammals and plants. Unfortunately, the chemical synthesis of these sugars from common sugars, despite the similarities between the two, remains challenging. The goal of this thesis is to expand the toolbox on the modification of common sugars, which will eventually lead to the efficient synthesis of useful rare sugars from common sugars

AIM and NPA Studies of the Role of Polarization in Electronic Structures

Atomic charges, as measured by Atoms in Molecule (AIM) or Natural Population Analyses (NPA), of the enolate anions of acetaldehyde and crotonaldehyde and of pentadienyl anion and cation show both charge transfer and polarization effects. In general, normal resonance structures and “curved arrow” symbolism give good representations of π-electron distributions, but back-polarizations in the σ-system complicate these electronic structures and can obscure the correspondence to resonance symbols. Twisting a vinyl group to orthogonality disrupts the π-system, but the vinyl group retains significant charge transfers and polarizations. The role of polarization is also demonstrated by the effect of external positive and negative charges on the electronic structure of ethylene. The π-electronic changes again are straightforward but are changed significantly by σ-polarizations. The polarizability of ethane is about half that of ethylene

Site-selective carbon-carbon bond formation in unprotected monosaccharides using photoredox catalysis

Site-selective photoredox reactions with somophiles readily enable branching of the carbon skeleton of unprotected glucosides, allosides, and xylosides regioselectively at C3. These reactions open the possibility of selective C-C bond formation in monosaccharides without multi-step protection-deprotection strategies

Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis

Despite its status as one of the world's most prevalent and deadly bacterial pathogens, Mycobacterium tuberculosis (Mtb) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover Mtb-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and N-6-tuberculosinyl adenosine (N-6-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and N-6-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels-Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome

Stereoselective Synthesis of 1‑Tuberculosinyl Adenosine; a Virulence Factor of <i>Mycobacterium tuberculosis</i>

Despite its status as one of the world’s most prevalent and deadly bacterial pathogens, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover <i>Mtb</i>-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and <i>N</i>⁶-tuberculosinyl adenosine (<i>N</i>⁶-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and <i>N</i>⁶-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels–Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome

CCDC 1481785: Experimental Crystal Structure Determination

Related Article: Jeffrey Buter, Dorus Heijnen, Ieng Chim Wan, F. Matthias Bickelhaupt, David C. Young, Edwin Otten, D. Branch Moody, Adriaan J. Minnaard|2016|J.Org.Chem.|81|6686|doi:10.1021/acs.joc.6b01332,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.