Spirodionic acid, a novel metabolite from Streptomyces sp., part 2: total synthesis through a twofold michael addition as a selective spiroannelation strategy.
To elucidate the structure of the new natural product spirodionic acid, which has three stereogenic centers of hitherto unknown configuration, two 4-ethenylspiro[4.5]dec-6-en-1,8-diones with opposite relative configuration at C4 and C5 were prepared. The first access involved the synthesis of 3-ethenyl-2-formylcyclopentanone (8) using a three-component coupling process. A sequence of Michael addition to penten-3-one (7) and intramolecular aldol condensation then led to the highly selective formation of the 4S*,5S*-configured spirocycle 5. In contrast, a selective spiroannelation of a cyclohexenone ring was accomplished by a novel type of twofold Michael addition to the dialkenyl ketone 11 with subsequent dehydrogenation to furnish the 4S*,5R*-configured spirocycle 25. Diastereoselective methylation and oxidative degradation then completed a highly efficient synthesis of the natural product as prerequisite for the assignment of its absolute configuration.
Siewert
Jürgen
J
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Textor
Adriana
A
Grond
Stephanie
S
von Zezschwitz
Paultheo
P
D000588:Amines / Q000737:chemistry; D002384:Catalysis; D003300:Copper; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
D000588:Amines; D007202:Indicators and Reagents; D013141:Spiro Compounds; C523960:spirodionic acid; D003300:Copper