0000000000297480
AUTHOR
Benjamin Meseguer
Naturstoffsynthese am polymeren Träger – Synthese und biologische Evaluierung einer Indolactam-Bibliothek
Als wirksame Aktivatoren der Proteinkinease C in Mausefibroblasten erwiesen sich einige Indolactam-V-Analoga 1, wie mit einem neuen biologischen Assay nachgewiesen wurde. Die Derivate dieses tumorpromovierenden Indolalkaloids wie auch der Naturstoff selbst wurden effizient durch eine kombinatorische Festphasensynthese hergestellt, deren Schlusselschritte eine regioselektive Aminierung des Indolrings und eine enantiodifferenzierende enzymatische Umsetzung sind.
An Efficient Stereoselective Synthesis of Stypodiol and Epistypodiol
An efficient synthesis of stypodiol (1) and its epimer at C-14, epistypodiol (2), was accomplished starting from (S)-(+)-carvone (7). The synthesis of both epimeric compounds proceeds through common intermediates using an IMDA reaction, a sonochemical Barbier reaction, and an acid-catalyzed quinol−tertiary alcohol cyclization as key synthetic steps.
Natural Product Synthesis on Polymeric Supports—Synthesis and Biological Evaluation of an Indolactam Library
Potent activators of protein kinase C in fibroblasts: This property was determined for several indolactam V analogues (1) with a new cell-based assay system. This tumor-promoting indole alkaloid and analogues thereof can be synthesized efficiently on the solid phase. The key steps of the combinatorial approach are a regioselective amination of the indole ring and an enantioselective enzymatic reaction.
Solid-Phase Synthesis and Biological Evaluation of a Teleocidin Library—Discovery of a Selective PKC Down Regulator
Protein kinaseC (PKC) is linked to the signal-induced modulation of a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis, and tumor development. The design and synthesis of small molecules that regulate these different cellular signaling systems is at the forefront of modern drug design. Herein we report a) an efficient method for the synthesis of indolactamV (6), a PKC activator, and its N13-des(methyl) analogues (19) using a regioselective organometallic transformation, a convenient aminomalonate derivative (10) to introduce the appropriate functionality and an enantiospecific enzymic hydrolysis as key steps; b) the use of this method in the first so…