New approaches towards the synthesis of the side-chain of mycolactones A and B

New approaches towards the synthesis of the C1' - C16' side-chain of mycolactones A and B from Mycobacterium ulcerans are reported. Chiral building block 4 ( Fig. 2) with the correct stereochemistry was obtained starting from naturally occurring monosaccharides, i.e. D-glucose or L-rhamnose. The polyunsaturated moiety 3 was synthesized in only 3 steps from 2,4-dimethylfuran. The building blocks were connected through a Sonogashira coupling resulting in the fast and convergent assembly of an 8,9-dehydro analogue 2 of the side-chain of mycolactones A and B. The synthesis of 1 is at this stage hampered by the lack of a selective partial hydrogenation protocol for alkynes embedded in a conjugated system. Alternative strategies involving palladium catalyzed sp(2) - sp2 coupling between C7' and C8' or C9' and C10' ( Fig. 1) were also explored

Collections & Connections

Collections & Connections is a newsletter of Western Kentucky University Libraries periodically featuring its major events. This Spring \u2703 issue highlights Southern Kentucky Festival of Books (now Southern Kentucky Book Fest), faculty and staff Jonathan Jeffrey, Ellen Micheletti, Jack Montgomery, Jennifer Small, and development officer Heather Slack-Ratiu

New approaches towards the synthesis of the side-chain of mycolactones A and B

New approaches towards the synthesis of the C1'–C16' side-chain of mycolactones A and B from Mycobacterium ulcerans are reported. Chiral building block 4 (Fig. 2) with the correct stereochemistry was obtained starting from naturally occurring monosaccharides, i.e. D-glucose or L-rhamnose. The polyunsaturated moiety 3 was synthesized in only 3 steps from 2,4-dimethylfuran. The building blocks were connected through a Sonogashira coupling resulting in the fast and convergent assembly of an 8,9-dehydro analogue 2 of the side-chain of mycolactones A and B. The synthesis of 1 is at this stage hampered by the lack of a selective partial hydrogenation protocol for alkynes embedded in a conjugated system. Alternative strategies involving palladium catalyzed sp2–sp2 coupling between C7' and C8' or C9' and C10' (Fig. 1) were also explored.

Catalytic asymmetric synthesis of enantiopure isoprenoid building blocks: application in the synthesis of apple leafminer pheromones

The first catalytic asymmetric procedure capable of preparing all 4 diastereoisomers (ee > 99%, de > 98%) of a versatile saturated isoprenoid building block was developed and the value of this new method was demonstrated in its application to the concise total synthesis of two pheromones.

Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with H2O2

A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H2O2 is described. High turnovers (>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only 1.5 equiv. of H2O2 with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.

CD1c Presentation of Synthetic Glycolipid Antigens with Foreign Alkyl Branching Motifs

Human CD1c is a protein that activates αβT cells by presenting self antigens, synthetic mannosyl phosphodolichols, and mycobacterial mannosyl phosphopolyketides. To determine which molecular features of antigen structure confer a T cell response, we measured activation by structurally divergent Mycobacterium tuberculosis mannosyl-β1-phosphomycoketides and synthetic analogs with either stereorandom or stereospecific methyl branching patterns. T cell responses required both a phosphate and a β-linked mannose unit, and they showed preference for C30–34 lipid units with methyl branches in the S-configuration. Thus, T cell responses were strongest for synthetic compounds that mimicked the natural branched lipids produced by mycobacterial polyketide synthase 12. Incorporation of methylmalonate to form branched lipids is a common bacterial lipid-synthesis pathway that is absent in vertebrates. Therefore, the preferential recognition of branched lipids may represent a new lipid-based pathogen-associated molecular pattern.

The unexpected role of pyridine-2-carboxylic acid in manganese based oxidation catalysis with pyridin-2-yl based ligands

A number of manganese-based catalysts employing ligands whose structures incorporate pyridyl groups have been reported previously to achieve both high turnover numbers and selectivity in the oxidation of alkenes and alcohols, using H2O2 as terminal oxidant. Here we report our recent finding that these ligands decompose in situ to pyridine-2-carboxylic acid and its derivatives, in the presence of a manganese source, H2O2 and a base. Importantly, the decomposition occurs prior to the onset of catalysed oxidation of organic substrates. It is found that the pyridine-2-carboxylic acid formed, together with a manganese source, provides for the observed catalytic activity. The degradation of this series of pyridyl ligands to pyridine-2-carboxylic acid under reaction conditions is demonstrated by 1H NMR spectroscopy. In all cases the activity and selectivity of the manganese/pyridyl containing ligand systems are identical to that observed with the corresponding number of equivalents of pyridine-2-carboxylic acid; except that, when pyridine-2-carboxylic acid is used directly, a lag phase is not observed and the efficiency in terms of the number of equivalents of H2O2 required decreases from 6–8 equiv. with the pyridin-2-yl based ligands to 1–1.5 equiv. with pyridine-2-carboxylic acid.

Oxidation of Alkenes with H2O2 by an in-Situ Prepared Mn(II)/Pyridine-2-carboxylic Acid Catalyst and the Role of Ketones in Activating H2O2

A simple, high yielding catalytic method for the multigram scale selective epoxidation of electron-rich alkenes using near-stoichiometric H2O2 under ambient conditions is reported. The system consists of a Mn(II) salt (<0.01 mol %), pyridine-2-carboxylic acid (<0.5 mol %), and substoichiometric butanedione. High TON (up to 300 000) and TOF (up to 40 s−1) can be achieved for a wide range of substrates with good to excellent selectivity, remarkable functional group tolerance, and a wide solvent scope. It is shown that the formation of 3-hydroperoxy-3-hydroxybutan-2-one from butanedione, and H2O2 in situ, is central to the activity observed.