Reactivity of 2-Nitropyrrole Systems: Development of Improved Synthetic Approaches to Nitropyrrole Natural Products

Abstract

Fundamental study of the reactivity of 2nitropyrrole systems has enabled the identification of effective methods for incorporation of this unusual motif into advanced natural product frameworks. The presence of electron-rich pyrrole N-protecting groups (BOM, Boz) was demonstrated to enable a variety of previously unsuccessful palladiummediated cross-couplings to be carried out in high yield. Based on this foundation, a series of regio-and stereoselective synthetic routes toward the nitropyrrolin and heronapyrrole families of natural products was developed by our group (G1−3). A full account of the strategic evolution of these approaches is reported here, highlighting the details of the setbacks encountered and eventual successes achieved en route, including the total synthesis of heronapyrrole B. The fundamental studies and completed total syntheses provide general access to the bioactive 2-nitropyrrole natural product manifold and also establish practical and efficient methods for preparation and elaboration of the medicinally relevant 2nitropyrrole motif.

A New, Rapid, Colorimetric Chemodosimeter, 4(pyrrol-1-Yl)pyridine, for Nitrite Detection in Aqueous Solution

“…NMR characterization of the final product proved to be problematic, though. It is common knowledge that pyrroles will react with nitro groups by irreversibly binding at the 2 position on the pyrrole ring [54,56], so this is a hypothesized final product due to the lack of other reagents in solution. However, the system is complicated by what appears to be the formation of an aggregate.…”

The Tetrahydrofuran Motif in Marine Lipids and Terpenes

“…Other synthetic approaches towards the 2-nitropyrrole system have been investigated by Brimble and Furkert, finding that Sonogashira coupling of 4-iodo-2-nitropyrrole with the appropriate alkyne was more effective than an approach relying on Stille coupling [ 42 ].…”

The Tetrahydrofuran Motif in Marine Lipids and Terpenes

“…Other synthetic approaches towards the 2-nitropyrrole system have been investigated by Brimble and Furkert, finding that sonogashira coupling of 4-iodo-2-nitropyrrole with the appropriate alkyne was more effective than an approach relying on Stille coupling [32].…”

“…(-)-Kumausallene (32) was isolated in 1983 from the marine red alga Laurencia nipponica Yamada [33]. This compound belongs to a family of non-isoprenoid sesquiterpenes that contain a 2,6-dioxa-bicyclo[3.3.0]octane core with an exo-cyclic bromoallene (Figure 9).…”