Parası kalmadığı için otobüse binemiyordur ailesi porno izle ona daha yeni para gönderdiği için tekrar porno istemeye utanınca mecburen otostop çekmek için youporn çantasını alarak yol kenarına gelir etekli porno liseli türk kız yol kenarında dururken yanına yaklaşan porno kibar bir gencin onu gideceği yere kadar bırakmak porno izle istemesine çok mutlu olur arabaya bindiklerinde gideceği yer ile porno arabayı kullanan adamın gittiği yer arasında çok mesafe sex izle farkı olduğunu anlayan türk kız bu yaptığı porno indir iyilik karşısında arabada ona memelerini açar porno sapıklaşan adam yol kenarındaki hotelde durarak porno izle üniversiteli otostop çeken türk kızına odada sakso çektirip sikerCondensed chiral heterocycles: Stereochemistry and activity| Abstract

Abstract

Condensed chiral heterocycles: Stereochemistry and activity

Author(s): Tibor Kurtn

The majority (~80%) of secondary metabolites are chiral and they occur as a single enantiomer containing five stereo genic elements in average. More than half of all the new approved drugs in the period 1981-2014 were derived directly or indirectly from natural products and the distribution of chiral drugs has increased from 30-40% in the 1990s to above 60% in the 2000s. In order to aid exploring the stereochemistry-activity and structure-activity relationship in natural products, the relative and absolute configuration of bioactive natural products have been determined by the combination of electronic (ECD) and vibrational circular dichroism (VCD), optical rotation (OR) and NMR measurements and quantum mechanical calculations. The potential of this approach is demonstrated on the examples of several complex natural products containing isolated blocks of stereogenic elements, e.g. both axial and central chirality or existing as stereoisomeric mixtures, which requires the combination of different approaches to differentiate more than two stereoisomers. For the efficient synthesis of molecular libraries consisting of condensed chiral O- and O,N-heterocycles with 4-6 rings, the scope of Knoevenagel-cyclization domino reactions is presented, which can afford novel complex skeletons from fairly simple starting materials in step- and atom-economic tranformations. Different mechanisms of domino sequences such as Knoevenagel-intramolecular hetero Diels- Alder (IMHDA), Knoevenagel-[1,5]-hydride shift-cyclization, Knoevenagel-[2+2] cycloaddition or Knoevenagel-Diels-Alder reactions are applied and explored to afford versatile condensed bioactive heterocycles. New multistep domino reactions are identified to increase the diversity of the compound library. Structure-activity and stereochemistry-activity relationships are studied in relation with antiproliferative, neuroprotective and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. 

 


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