TOTAL SYNTHESIS OFDISCODERMOLIDE有機合成化学特論 発表資料2012-01-06 有末 芳 (M1)
Isolation: Gunasekera (1990)Yield: 0.002wt% (7 mg/454 g of sponge)Biological Activity: Discodermia dissoluta Immunosuppression Antifungal Microtubule Stabilization (MTS agent)Important Profiles:• Acts more faster and powerful than any other MTS agents. Cancer Cell and• Effective against multi-drug (include Taxol) resistant cell lines. Its Apoptosis• High water solubility (100-fold greater than Taxol)• Unique action mechanism, etc… Very attracted compound !!! Isolation: JOC 1990, 55, 4912. For action of mechanism, see: ACIE 1998, 37, 2014.
1990 Gunasekera Isolation1993 Schreiber First total synthesis ((–)-form) Established absolute configuration1994 Schreiber First natural (+)-enantiomer synthesis1995 Smith (–)1997 Myles (–)1998 Marshall (+)1999 Smith Gram-scale synthesis2000 Paterson Novel approach2002 Paterson 2nd generation2003 Smith 2nd generation2003 Novartis Process synthesis Phase I clinical trials2005 Panek (+)
What are most effective? 1. Aldol 2. Allylboronate/allylborane addition to aldehyde 3. Ireland-Claisen 4. Diels-AlderMarshall’s concept: chiral allenylmetal methodology (variant of 2) JOC 1998, 63, 817