Biomedical subjects
Publications and source records attributed to Dirk Trauner.
[reaction: see text] Concise total syntheses of the bioactive polypropionates aureothin, N-acetylaureothamine, and aureonitrile are described.
[reaction: see text] The total synthesis of bicyclo[4.2.0]octane natural products elysiapyrones A and B is described.
The total synthesis of naphthoquinone natural products isolated from the Bignoniaceae plant family is described. Pinnatal, isopinnatal, sterekunthals A and B, pyranokunthones A and B, and anthrakunthone have been prepared along the lines of a biosynthetic proposal involving pericyclic reactions as key steps. The first case of catalysis in oxa 6pi electrocyclizations is reported.
Intramolecular cycloadditions of 5-vinyl-1,3-cyclohexadienes were studied with B3LYP/6-31G(d) density functional calculations. The one-atom tether dictates that the Z substituent becomes exo and the E substituent becomes endo in the TS. The geometry of the cycloaddition TS is typical of a pericyclic transformation except unusual twisting of the dienophile places the endo substituent in a relatively steric-free position and the exo substituent in a highly crowded position. The experimental rate differences between isomeric pairs of vinylcyclohexadienes can be explained by comparing reactant destabilization when a bulky group occupies the Z position of the starting alkene and transition state stabilization when a bulky group is endo in the cycloaddition TS.
The biomimetic synthesis and full structural elucidation of rubicordifolin, a cytotoxic natural product isolated from Rubia cordifolia, is described.
Members of a family of alpha-methoxy-gamma-pyrone-containing polypropionate natural products have been stereoselectively synthesized. Two key iodovinyl pyrone building blocks were coupled to appropriately selected vinyl stannanes to assemble the highly substituted polyene side chains of the natural products. [structure: see text]
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Various strategies have been developed recently for imparting light sensitivity onto normally insensitive cells. These include expression of natural photosensitive proteins, photolysis of caged agonists of native cell surface receptors and photoswitching of isomerizable tethered ligands that act on specially engineered ion channels and receptor targets. The development of chemical tools for optically stimulating or inhibiting signaling proteins has particular relevance for the nervous system, where precise, noninvasive control is an experimental and medical necessity.
Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K(+) channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration.
The development of catalytic asymmetric Nazarov reactions that require only 10 mol % of chiral Lewis acid and proceed with ee's between 72% and 97% is described.
The total synthesis of the molluscan polypropionate (-)-crispatene is described. The synthesis features a palladium-catalyzed cross-coupling to establish a sensitive conjugated tetraene and its Lewis acid-catalyzed cycloisomerization to yield the bicyclo[3.1.0]hexene core of the natural product. The absolute configuration of (-)-crispatene and related molecules is established.
Recent investigations have shown that a range of small molecules that reflect the metabolic state of a cell regulate the activity of potassium channels. For instance, hydrogen peroxide has been shown to activate adenosine 5'-triphosphate-sensitive potassium channels (K(ATP) channels), whereas heme closes certain calcium-activated potassium channels. Although the exact function of the beta subunit associated with voltage-gated potassium channels is still unclear, its crystal structure suggests that membrane excitability is directly coupled to metabolism.
Expeditious and high-yielding Nazarov cyclizations of 2-alkoxy-1,4-pentadien-3-ones are described. An example of a catalytic asymmetric Nazarov cyclization is presented. [reaction: see text]
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[reaction: see text]. An asymmetric approach toward the [6-7] ring system of the guanacastepenes is described.
The rational design and development of four-fold symmetrical ligands for potassium channels is described.
[reaction: see text] The stereoselective cyclization of delta-hydroxy nitriles to afford N,O-acetals and the application of this reaction toward the synthesis of glycosylamines is described.