Synthetic Studies on FNC-RED and Its Analogues Containing an All syn-Cyclopentanetetrol Moiety

Abstract

FNC-RED exhibits innate immune receptor Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD2) stimulatory activity. We have developed a divergent synthetic route to FNC-RED derivatives containing various alkyl side chains. Key features of the synthetic study include stepwise palladium catalyzed cross-coupling reactions and the construction of an all syn-cyclopentanetetrol moiety.

Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes that Form the All-cis Cyclopentanetetraol Moiety

“…To date, total syntheses of 1 and 2 have not been reported. 19,20 The biosynthetic gene cluster (BGC) for either compound has not been characterized either. Examining the structure of 2, the pyridone and pyran portions of the molecule are nearly identical to that found in the known mycotoxin (−)-sambutoxin (3) (Figure 1B).…”

“…Both compounds show significant antifungal activity by inhibiting mitochondrial cytochrome bc 1 complex. , The defining structural feature of 1 and 2 is the all- cis cyclopentanetetraol moiety that is connected to the 5-position of a N- methyl-3-pyranyl-4-hydroxy-2-pyridone. To date, total syntheses of 1 and 2 have not been reported. , The biosynthetic gene cluster (BGC) for either compound has not been characterized either. Examining the structure of 2 , the pyridone and pyran portions of the molecule are nearly identical to that found in the known mycotoxin (−)-sambutoxin ( 3 ) (Figure B) .…”