PubMed Health⌕ Search

Biomedical subjects

Sabine Laschat

Publications and source records attributed to Sabine Laschat.

6 recordsLinked to original sources
PubMed2006

Total synthesis and NMR investigations of cylindramide.

Cylindramide (1) was built up from three components: a hydroxyornithine derivative 7, a tetrazolylsulfone 8, and a substituted pentalene subunit 9. Derivative 7 was prepared in a six-step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N-Boc-3-aminopropanal (12). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22. The synthesis of the pentalene fragment 9 started from cycloocta-1,5-diene 26, that was converted into enantiopure bicyclo[3.3.0]octanedione 29. The latter was functionalized to give derivative 9. The total synthesis was accomplished by inducing C-C bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia-Kocienski conditions, macrocyclization, and subsequent Lacey-Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1H and 13C NMR spectroscopic investigations (DQF-COSY, ROESY spectra), the stereochemistry of synthetic cylindramide (1) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest-energy structures for cylindramide.

Amides↗
PubMed2006

Columnar and smectic liquid crystals based on crown ethers.

Unsymmetrical benzo[15]crown-5 ethers 5 with one lateral ortho-terphenyl unit bearing alkoxy side chains of varying chain lengths (C5-C14) were prepared from 3,4-dialkoxyphenylbromides 2. Complexation with metal salts MX (M = Na, Cs) afforded the corresponding derivatives MX5. The uncomplexed crown ethers 5 h and 5 i, with dodecyloxy and tetradecyloxy side chains, respectively, exhibit liquid crystalline properties. In the series of complexed crown ethers, liquid crystal properties appeared as early as NaI5 f with C9H19 side chains. Whereas the uncomplexed 5 h,i form smectic mesophases, the complexed NaI5 g and NaI5 h exhibit textures typical of columnar mesophases. These results were supported by X-ray diffraction measurements (WAXS, SAXS), which revealed smectic (5 h,i), rectangular columnar (NaI5 g), and hexagonal columnar (NaI5 h) mesophases. As the liquid crystalline phase might retain packing features of the solid-state structure, single-crystal X-ray analyses were also performed for some of the uncomplexed and complexed crown ether derivatives. The complex NaI(3)5 a displays a sandwich-type structure, with the crown ether cores mutually antiperiplanar and maintaining an almost perfect crown conformation. In contrast, non-mesogenic uncomplexed crown ether 5 b displays a layer-type ordering in the solid phase.

Journal Article↗
PubMed2006

Total synthesis and biological evaluation of (-)-pectinatone employing a methyl-branched wax ester as key building block.

Unnatural (-)-pectinatone ((-)-3) was prepared in five steps starting from the highly methyl-branched wax ester 4, employing bromination of the ester enolate and subsequent base-induced elimination to the enoate 6 as the key step. Both (-)-3 and the amides 8b and 8c, which were isolated as by-products in the reaction sequence, displayed antimicrobial activity and cytotoxicity.

Animals↗
PubMed2005

Synthesis and DNA binding properties of novel benzo[b]isoquino[2,3-h]-naphthyridines.

Several benzo[b]isoquino[2,3-h]-naphthyridines have been prepared via formal hetero-Diels Alder reaction of N-aryl imines as a key step. These compounds have different side chains at C-11, and a cis or trans configuration at the C-8a,C-14a ring junction. Binding constants for the interaction with oligonucleotides and polynucleotides were determined by UV absorption and melting experiments. NMR experiments (NOE) revealed that the cis isomers, showing a slightly folded structure, preferentially bind to the minor groove of AT-rich oligomers. In contrast, the trans isomers prefer the CG-rich sequences, leading to cap-complexes with the isoquinoline moiety stacked at the top of the double helix, in agreement with the flatter shape, and with a preference for the 3'-terminals, as found for camptothecins. Models of the complexes were built up by molecular dynamics (MD) calculations, by using the inter-proton distances derived from the NOE values. Cytotoxicity assays against human Ewing sarcoma cell lines RD-ES and CAD-ES1 were performed.

Cell Line, Tumor↗
PubMed1996

Preparation of 2,3,4-Trisubstituted Piperidines by a Formal Hetero-Ene Reaction of Amino Acid Derivatives.

N-Benzyl- or N-tosyl-N-(4-methyl-3-pentenyl)amino aldehyde benzylimines, which are obtained from alanine, leucine, or phenylalanine methyl esters in five steps, can be cyclized diastereoselectively in the presence of Lewis acids to give 3-amino-2,4-dialkyl-substituted piperidines. The product distribution and diastereoselectivity depends on the type of Lewis acid and nitrogen-protecting group. Benzyl-protected imines give 2-alkyl-3-(benzylamino)-4-isopropenyl piperidines with FeCl(3) and 2-alkyl-3-(benzylideneamino)-4-isopropylpiperidines with TiCl(4). Tosyl-protected imines show a decreased level of selectivity. The relative configurations of the piperidines were established by NMR and X-ray crystal structure analyses. Iminium ion cyclization followed by two competitive ionic pathways, i.e. either proton elimination or hydride transfer are discussed for these reactions.

Journal Article↗