110815-32-2Relevant academic research and scientific papers
Solid-phase synthesis and biological evaluation of a teleocidin library - Discovery of a selective PKCδ down regulator
Meseguer, Benjamin,Alonso-Diaz, Daniel,Griebenow, Nils,Herget, Thomas,Waldmann, Herbert
, p. 3943 - 3957 (2007/10/03)
Protein kinase C (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 indolactam V (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 solid-phase synthesis of a teleocidin library modifying the N-13, C-12 and C-7 alkyl chains, and, therefore, producing a library of potential activators and/or inhibitors of PKC of the general structure (32); c) the activation of PKC by selected members of the library using a MARCKS translocation in vivo assay system; d) the observation that some of these analogues are nearly as effective as the natural PKC activators phorbol dibutyrate and (-)-indolactam V (6), and e) the observation that some of these analogues have different potential to induce down-regulation of members of the PKC gene family after chronic stimulation.
Natural product synthesis on polymeric supports - Synthesis and biological evaluation of an indolactam library
Meseguer, Benjamin,Alonso-Diaz, Daniel,Griebenow, Nils,Herget, Thomas,Waldmann, Herbert
, p. 2902 - 2906 (2007/10/03)
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.
A Regio- and stereocontrolled total synthesis of (-)-indolactam-V
Kogan, Timothy P.,Somers, Todd C.,Venuti, Michael C.
, p. 6623 - 6632 (2007/10/02)
(-)-Indolactam-V (IL-V) (1)-was prepared in 10 steps from L-tryptophan methyl ester in 17.1% overall yield. The key steps involve regiospecific thallation of the acylindole intermediate (4), followed by azide displacement and reduction to introduce the 13-amino group. Control of the C-11 stereocenter was achieved by SN2 displacement of the chiral inflate (10), derived from D-valine. The thallium mediated closure of dipeptide (17) did not provide an alternative route to IL-V.
SYNTHETIC STUDIES ON TELEOCIDIN IV. AN EFFICIENT SYNTHESIS OF (-)-INDOLACTAM V
Nakatsuka, Shin-ichi,Masuda,Toshiya,Sakai, Kunisaku,Goto, Toshio
, p. 5735 - 5738 (2007/10/02)
An efficient synthesis of (-)-indolactam V (3) was achieved in 12 steps starting from L-tryptophan.
