This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-9-243.pdf

The chemistry of isoindole natural products

We report geometry-dependent cyclizations of o-alkynylaryl ketoximes and nitrones catalyzed by gold complexes. (E)-Ketoximes undergo N-attack to give isoquinoline-N-oxides. In sharp contrast, (Z)-ketoximes undergo unprecedented O-nucleophilic attack, followed by a redox cascade leading to a novel catalytic entry to isoindoles of diverse scope. The structure of an isoindole was unambiguously supported by X-ray crystallography. We demonstrated the generality of the isoindole synthesis from either (Z)-oximes or nitrones, and presented a mechanistic model of this redox cascade based on the reaction profiles of various substrates.

Geometry-dependent divergence in the gold-catalyzed redox cascade cyclization of o-alkynylaryl ketoximes and nitrones leading to isoindoles

A general method for the synthesis of difluorobora-diisoindolomethene dyes with phenyl, p-anisole, or ethyl-thiophene substituents has been developed. The nature of the substituents allows modulation of the fluorescence from 650 to 780 nm. Replacement of the fluoro ligands by ethynyl-aryl or ethyl residues is facile using Grignard reagents. Several X-ray molecular structures have been determined, allowing establishment of structure–fluorescence relationships. When the steric crowding around the boron center is severe, the aromatic substituents α to the diisoindolomethene nitrogens are twisted out of coplanarity, and hypsochromic shifts are observed in the absorption and emission spectra. This shift reached 91 nm with ethyl substituents compared to fluoro groups. When ethynyl linkers are used, the core remains flat, and a bathochromic shift is observed. All the fluorophores exhibit relatively high quantum yields for emitters in the 650–800 nm region. When perylene or pyrene residues are connected to the dy...

Chemistry at boron: synthesis and properties of red to near-IR fluorescent dyes based on boron-substituted diisoindolomethene frameworks.

Publisher Summary This chapter discusses the properties and synthesis of isoindoles. Isoindole is a white solid which becomes discolored and resinous at room temperature, especially in the presence of air. It may be handled for short periods using vacuum techniques, or in solution under an inert atmosphere. The synthesis of isoindoles includes: (1) syntheses from isoindolines, (2) retro-cycloadditions, (3) syntheses from phthalimidines and related compounds, (4) syntheses from ortho-disubstituted benzenes, (5) routes from pyrroles, and (6) rearrangements and other reactions. The absorption spectra of isoindoles exhibits a series of strong bands in the near ultraviolet region extending in cases of further conjugation almost into the visible region. The kinetic instability of isoindoles dominates the chemistry of the simple systems and is principally to be ascribed to autoxidation and self-condensation reactions. Many isoindoles readily form Diels–Alder adducts by reaction across the electron-rich 1,3-positions with dienophiles. Isoindoles are readily oxidized; as with pyrroles, the products are often colored, poorly characterized, polymeric materials.

The Chemistry of the Isoindoles

Substitution and addition reactions of isoindoles

o-Acyl-benzophenone (3), zuganglich aus 3-Alkyl-phthaliden durch Umsetzung mit Phenyl-magnesiumbromid und anschliesende Luftoxydation, liefern mit Ammoniumsalzen in schwach sauren Medien tiefblaue, kristallisierte Farbstoffe, die 5.5′-Diphenyl-3.4;3′.4′-dibenzo-pyrromethene-(2.2′) (5) darstellen. Der Mechanismus der Farbstoffbildung wird diskutiert, wobei die aus 3 und Ammoniak erhaltenen 1-Hydroxy-3-alkyl-1-phenyl-isoindolenine (8) als Zwischenprodukte eine Rolle spielen.

Setuko Sugiyama

Papers

Konstitution der Farbstoffe aus o ‐Acyl‐benzophenon und Ammoniak