Ein einheitlicher Ansatz zur stereoselektiven Totalsynthese von Pyridonalkaloiden und deren neuritogene Aktivität

Abstract

Ein Weg für alle: Die Entwicklung von Substanzen, die Neuritenwachstum induzieren, könnte ein wertvoller Ansatz zur Entdeckung potenzieller Medikamente gegen neurodegenerative Krankheiten sein. Mithilfe eines difunktionellen Bausteins gelang die Totalsynthese einer ganzen Reihe von entomopathogenen Pilzen produzierter Pyridonpolyen‐Naturstoffe, welche die Differenzierung von PC‐12‐Zellen verursachen.

Cover Picture: Reduction of Charge and Discharge Polarization by Cobalt Nanoparticles‐Embedded Carbon Nanofibers for Li–O2 Batteries (ChemSusChem 15/2015)

“…The mixture was then warmed to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether/Et 2 O, 97:3) to give ester ( S )‐ 10 (776.6 mg, 67 %). The spectroscopic data for compound ( S )‐ 10 were identical to those described in the literature 8…”

“…in the presence of tetrapropylammonium perruthenate (TPAP; 0.03 equiv. ), in order to suppress the racemisation of the aldehyde intermediate, to produce (2 E ,4 S )‐ethyl 2,4‐dimethylhex‐2‐enoate [( S )‐ 10 ] in 67 % yield 8. Reduction of ( S )‐ 10 with DIBAL (diisobutylaluminum hydride) gave alcohol ( S )‐ 11 , whose subsequent oxidation with PCC (pyridinium chlorochromate) produced the corresponding aldehyde [i.e., ( S )‐ 9 ] 8.…”

“…), in order to suppress the racemisation of the aldehyde intermediate, to produce (2 E ,4 S )‐ethyl 2,4‐dimethylhex‐2‐enoate [( S )‐ 10 ] in 67 % yield 8. Reduction of ( S )‐ 10 with DIBAL (diisobutylaluminum hydride) gave alcohol ( S )‐ 11 , whose subsequent oxidation with PCC (pyridinium chlorochromate) produced the corresponding aldehyde [i.e., ( S )‐ 9 ] 8. This aldehyde was treated with oxazolidin‐2‐one (+)‐( S )‐ 12 and catalytic amounts of MgCl 2 and NaSbF 6 9 to give anti aldol product (6″ S )‐ 14 in 38 % yield and with 88 % dr 10.…”

“…Commercially available (±)‐2‐methylbutan‐1‐ol was subjected to one‐pot oxidation/olefination using the TEMPO–BAIB [2,2,6,6‐tetramethylpiperidin‐1‐oxyl and bis(acetoxy)iodobenzene] system and (carbethoxyethylidene)triphenylphosphorane17 to give (±)‐( E )‐ethyl 2,4‐dimethylhex‐2‐enoate [(±)‐ 10 ] in 61 % yield 18. Reduction of (±)‐ 10 with DIBAL and subsequent oxidation with PCC produced the corresponding aldehyde [i.e., (±)‐ 9 ] 8. This aldehyde was treated with oxazolidin‐2‐one [(+)‐ 12 ] and catalytic amounts of MgCl 2 and NaSbF 6 9 to give a 1:1 mixture of anti aldols (6″ R )‐ 13 and (6″ S )‐ 13 after methanolysis of the silyloxy derivatives (6″ R )‐ 14 and (6″ S )‐ 14 (Scheme ).…”

Neurotrophic Natural Products: Chemistry and Biology

“…[279] More recently, a divergent synthesis of various neurotrophic pyridone alkaloids was reported by Gademann and co-workers. [275d,280] The related farinosone C ( 290 ) [277] also promotes neurite outgrowth in NGF-mediated PC-12 cell lines at a concentration of 50 μM. [281] The authors reported a synthesis of 290 and have disclosed that L-tyrosinolamide represents its pharmacophore.…”