Substituted 2,2′-bipyrroles and pyrrolylfurans via intermediate isoxazolylpyrroles

Abstract

We describe a new synthesis of the 3-chloro-(4′-methoxy)-2,2′-pyrrolylfuran segment (3) of (+)− roseophilin. The route exploits a isoxazoylpyrrole intermediate, wherein the isoxazole ring serves as a β-diketone equivalent and a directing group for palladium catalyzed chlorination of the attached pyrrole. Subsequent reduction of the N–O bond and acid promoted cyclization afords roseophilin segment 3b in five steps and 19% overall yield. This strategy was extended to the synthesis of 3-chloro-(4′-alkoxy)-2,2′-pyrrolylfurans (16a–c) and 4-alkoxy-2,2′-bipyrroles (20a–c), which are building blocks to synthesize bioactive prodiginine natural products and their congeners.

β‐Cyclodextrin–Glycerol Dimers: Synthesis and NMR Conformational Analysis

“…These reactions have been highlighted in the total synthesis of seragakinone A, allowing one to set the all‐carbon quaternary center at the angular position in the synthesis of this complex natural product (Scheme C) 134. The above examples published by the Suzuki group (Scheme and Scheme )131–134 together with the recently reported applications of isoxazoles in the synthesis of tetracyclines by the Myers group (Scheme B)6a–f and in the synthesis of roseophilin by the Harran group (not shown)6j,k constitute some of the outstanding examples of the application of this ring system in total synthesis.…”

Anomalous Chromophore Disruption Enables an Eight-Step Synthesis and Stereochemical Reassignment of (+)-Marineosin A

“…When ketones 6 and bipyrrole 20 were dissolved in anhydrous MeOH and treated with HCl, the solution turned deep red within seconds. This was consistent with condensation product 21 (Scheme ) being formed.…”

[3+2] Cycloaddition of Tosylmethyl Isocyanide with Styrylisoxazoles: Facile Access to Polysubstituted 3-(Isoxazol-5-yl)pyrroles

“…In this context, isoxazole substituted pyrroles are present as the core substructure in some meaningful compounds, such as isoxazolylpyrroles I and II are inhibitors to oral and mouth cancer cell and the activators to cellular tumor antigen p53 [ 2 , 3 ]. Isoxazolylpyrroles III and IV are the key intermediates in the synthesis of bioactive prodiginines natural products and their congeners, and the precursors structures of phosphodiesterase inhibitors PDE-I and PDE-II, which inhibitory activity toward cyclic adenosine-3′,5′-monophosphate phosphodiesterase, respectively [ 4 , 5 ]. Isoxazolylpyrroles V is a receptor for recognition and sensing purposes in aprotic solvents [ 6 , 7 ].…”