P-55 GKK1032類のエナンチオ選択的全合成研究(ポスター発表の部)

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GKK1032s are novel antimicrobial antibiotics, which were isolated from the fermentation broth of a fungus, Penicillium sp. GKK1032. As closely related natural products, pyrrocidines were also isolated, which were found to possess inhibitory activities against Gram-positive bacteria. The structures of GKK1032s and pyrrocidines were determined by NMR spectral analysis, although their absolute configurations remain unclear. These natural products consist of a decahydrofluorene skeleton with nine stereogenic centers and a fused 13-membered macrocycle, including an aryl ether and a pyrrolidinone ring. The total synthesis of GKK1032s and pyrrocidines were expected to be accomplished by a union of the decahydrofluorene units and the bicyclic lactam units. An intramolecular Diels-Alder (IMDA) approach was expected as a key step for the construction of the decahydrofluorene units. Starting from the Diels-Alder adduct 3 of trans-2-methyl-1,3-pentadiene 1 and maleic anhydride 2, a key racemic γ-acetoxy-γ-lactone 6 was synthesized. The enzymatic kinetic resolusion of the racemate 6 was efficiently achieved to afford highly enantioenriched (+)-5 and (+)-6. The absolute stereochemistries of (+)-5 and (+)-6 were unambiguously determined by chemical modifications. The γ-hydroxy-γ-lactone (+)-5 was converted to two IMDA substrates 14 and 15 via 7-9 and 13. The thermal IMDA reaction of 15 provided a fully functionalized decahydrofluorene derivative (-)-17 stereoselectively. The synthesis of the bicycle lactam part 22 was accomplished from 4-hydroxybenzaldehyde 18, which was converted to γ-ketocarboxylic acid 21, followed by the coupling reaction with (S)-(-)-2-phenylglycinol. The aldol reaction of 22 and 23 derived from (-)-17 proceeded without event to afford the desired macrocyclization substrate 24
2006-09-15

P-55 GKK1032類のエナンチオ選択的全合成研究(ポスター発表の部)

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