[Show abstract][Hide abstract] ABSTRACT: The stereospecific BF3-mediated α-ketol rearrangement of β-hydroxy-α-ketoamides yields isolable 2-difluoroboranyloxy-3-keto-amides. X-ray and NMR analysis reveal a carbonyl coordination of the boron by the amide not the ketone. The boron complexes are air-stable solids, can be purified by silica gel chromatography, and exhibit novel reactivity in bromination and superior stereoselectivity in dipolar cycloaddition reactions.
[Show abstract][Hide abstract] ABSTRACT: The adsorption of diethyl ether (Et2O) on Si(001) was studied by means of scanning tunneling microscopy (STM) and photoelectron spectroscopy. Et2O reacts on Si(001) via a datively bonded intermediate, which was isolated at surface temperatures below 100 K. At higher surface temperature, Et2O converts dissociatively into the final state by cleaving one O-C bond; the resulting −O-C2H5 and −C2H5 fragments are found to attach on two Si dimers of neighboring dimer rows. Tip-induced hopping of the −C2H5 fragment on one dimer was observed at positive sample bias. The results are discussed in the context of recent experiments on the reaction of tetrahydrofuran (THF) on Si(001) (Mette et al. ChemPhysChem 2014, 15, 3725) and allow a more general description of the reaction of ethers on Si(001).
The Journal of Physical Chemistry C 03/2015; 119(11):6018-6023. DOI:10.1021/jp511780p · 4.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 2-unsubstituted indole adds under Cu-box-catalysis to mesoxalic ester amides with high enantioselectivity, whereas low enantiomeric excess is obtained for 2-substituted indoles. A mesoxalic ester amide is used as key component in the total syntheses of alkaloids cladoniamide G and cladoniamide F. The natural product syntheses involve Suzuki cross-coupling to a 2,2′-biindole, arylation of the vic-tricarbonyl compound, and intramolecular lactam formation.
European Journal of Organic Chemistry 03/2015; 2014(24). DOI:10.1002/ejoc.201402531 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The reaction of tetrahydrofuran (THF), an otherwise inert solvent molecule, on Si(001) was experimentally studied in ultrahigh vacuum. Using scanning tunneling microscopy (STM) and photoelectron spectroscopy at variable temperature, we could both isolate a datively bound intermediate state of THF on Si(001), as well as the final configuration that bridges two dimer rows of the Si(001) surface after ether cleavage. The latter configuration implies splitting of the O-C bond, which is typically kinetically suppressed. THF thus exhibits a hitherto unknown reactivity on Si(001).
[Show abstract][Hide abstract] ABSTRACT: The total synthesis of the heptacyclic natural product isoquinocyclinone has been achieved. A Hauser annulation was used to assemble the anthraquinone core structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was prepared by alkyne addition to a lactone intermediate and subsequent Ni0-mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and final intramolecular N-alkylation.
Chemistry - A European Journal 09/2014; 20(36). DOI:10.1002/chem.201403880 · 5.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Porins, like the outer membrane protein G (OmpG) of Escherichia coli, are ideal templates amongst ion channels for protein and chemical engineering due to their robustness and simple architecture. OmpG shows fast transitions between open and closed states, which were attributed to loop 6 (L6). As flickering limits single-channel based applications, we pruned L6 by either 8 or 12 amino acids. While the open probabilities of both L6 variants resemble that of native OmpG, their gating frequencies were reduced by 63% and 81% respectively. Using the 3.2 Å structure of the shorter L6 variant in the open state we engineered a minimal porin (220 aa), where all remaining extramembranous loops were truncated. Unexpectedly, this minimised porin still exhibited gating albeit fivefold less frequent than OmpG. The residual gating of the minimal pore is hence independent of L6 rearrangements and involves narrowing of the ion conductance pathway most probably driven by global stretching-flexing deformations of the membrane-embedded β-barrel.
[Show abstract][Hide abstract] ABSTRACT: A synthesis of the 9-epimer of the marine natural product wailupemycin A is reported. The key reaction sequence consists of a diastereoselective enamine addition to a tricarbonyl monohydrate, the formation of an enol silyl acetal, and finally the stereocontrolled addition of the a-pyrone substructure.
[Show abstract][Hide abstract] ABSTRACT: The Passerini reaction of vic‐diketo amides with a variety of isocyanides and carboxylic acids has been examined. α‐Acyloxy β‐keto carboxamides were formed regioselectively as the major products. For the Passerini reactions with electron‐withdrawing‐group‐substituted acetic acids, a one‐pot Passerini–Knoevenagel reaction was accomplished by the addition of triethylamine. vic‐Diketo amides react with a variety of isocyanides and carboxylic acids in a regioselective Passerini three‐component reaction (P‐3CR) to give good to excellent yields of α‐acyloxy‐β‐keto‐carboxamides. In the case of Passerini reactions with electron‐withdrawing‐group‐substituted acetic acids, a one‐pot Passerini–Knoevenagel reaction was accomplished by the addition of triethylamine.
European Journal of Organic Chemistry 02/2014; 2014(5). DOI:10.1002/ejoc.201301548 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine is reported. The tetrasubstituted dibenzofuran substructure was accessible either through a Pd-mediated ortho-metalation or by an Ir-catalyzed meta-borylation. The synthesis of the β,β,α-linked trisaccharide consisting of D-olivose, L-rhodinose, and L-rhamnose was challenged by the unprecedented β-linked rhodinose. A Pd-catalyzed β-selective glycosylation of a 4-epi-rhodinose and a subsequent Mitsunobu inversion provided selectively the β-linked L-rhodinose-L-rhamnose disaccharide. Comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product.
Chemistry - A European Journal 06/2013; 19(23). DOI:10.1002/chem.201204545 · 5.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ion channels provide a conductance pathway for the passive transport of ions across membranes. These functional molecules perform key tasks in biological systems such as neuronal signaling, muscular control, and sensing. Recently, function-oriented synthesis researchers began to focus on ion channels with the goal of modifying the function of existing ion channels (ion selectivity, gating) or creating new channels with novel functions. Both approaches, ion channel engineering and de novo design, have involved synthetic chemists, biochemists, structural biologists, and neurochemists. Researchers characterize the function of ion channels by measuring their conductance in samples of biological membranes (patch clamp) or artificial membranes (planar lipid bilayers). At the single molecule level, these measurements require special attention to the purity of the sample, a challenge that synthetic chemists should be aware of. Ideally, researchers study the function of channels while also acquiring structural data (X-ray, NMR) to understand and predict how synthetic modifications alter channel function. Long-term oriented researchers would like to apply synthetic ion channels to single molecule sensing and to implantat these synthetic systems in living organisms as tools or for the treatment of channelopathies. In this Account, we discuss our own work on synthetic ion channels and explain the shift of our research focus from a de novo design of oligo-THFs and oligo-THF-amino acids to ion channel engineering. We introduce details about two biological lead structures for ion channel engineering: the gramicidin β(6,3) helix as an example of a channel with a narrow ion conductance pathway and the outer membrane porins (OmpF, OmpG) with their open β-barrel structure. The increase and the reversal of ion selectivity of these systems and the hydrophobic match/mismatch of the channel with the phospholipid bilayer are of particular interest. For engineering ion channels, we need to supplement the single-point attachment of a synthetic modulator with the synthesis of a more challenging two-point attachment. The successful function-oriented synthesis of ion channels will require interdisciplinary efforts that include new electrophysiology techniques, efficient synthesis (peptide/protein/organic), and good structural analysis.
Accounts of Chemical Research 05/2013; 46(12). DOI:10.1021/ar400007w · 24.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 6,13-Disubstituted pentacenes were synthesized. Their electrochemical and optical properties, in addition to their packing motifs in the solid state, were determined. Treatment of pentacenequinone with TMSCF3 (Ruppert's reagent) and deprotection led to 6,13-bis(trifluoromethyl)pentacene-6,13-diol, which was aromatized to 6,13-bis(trifluoromethyl)pentacene by using PBr3. 6,13-Dialkoxypentacenes were accessible by alkylation of the corresponding hydroquinopentacenes by using dialkyl sulfates. 6,13-Bis(trifluoromethyl)pentacene and 6,13-dimethoxypentacene exhibit slipped face-to-face π stacking in the solid state, whereas 6,13-diethoxypentacene forms pairs of π-stacking molecules in the solid state.
European Journal of Organic Chemistry 03/2013; 2013(9). DOI:10.1002/ejoc.201201714 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Crotylboration of vic-diketoamides and vic-diketo esters was achieved with high diastereoselectivity and complementary regioselectivity. Whereas (E)-crotylboration of α,β-diketoamides resulted in high yields (91-99 %) of β-crotylated products obtained as a single diastereomer (anti), Lewis acid promoted crotylboration of α,β-diketo esters yielded the α-crotylated species with the anti product as main diastereomer. (E)-Crotylboration of α,β-diketoamides resulted in high yields (91-99 %) of β-crotylated products obtained as a single diastereomer (anti). Lewis acid promoted crotylboration of α,β-diketo esters yielded the α-crotylated species with the anti product as main diastereomer.
European Journal of Organic Chemistry 02/2013; 2013(4). DOI:10.1002/ejoc.201201517 · 3.15 Impact Factor