communesin-b and perophoramidine

The communesin/nomofungin/perophoramidine story is an impressive example of how biogenetic considerations can lead to the correction of structural misassignments and inspire synthetic chemists with new, fruitful ideas. Intensive studies by a number of research groups culminated in the total synthesis of perophoramidine by the Funk research group in 2004. In 2007, Qin and co-workers completed the first total synthesis of a communesin.

Topics: Alkaloids; Carbazoles; Epoxy Compounds; Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Molecular Structure; Penicillium

We report a full account of our work towards the development of Mo-catalyzed asymmetric allylic alkylation reactions with 3-alkyloxindoles as nucleophiles. The reaction is complementary to the Pd-catalyzed reaction with regard to the scope of oxindole nucleophiles. A number of 3-alkyloxindoles were alkylated successfully under mild conditions to give products with excellent yields and good-to-excellent enantioselectivities. Applications of this method to the preparation of indoline alkaloids such as (-)-physostigmine, ent-(-)-debromoflustramine B, and the indolinoquinoline rings of communesin B are reported.

Topics: Alkaloids; Alkylation; Catalysis; Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Indoles; Molecular Structure; Molybdenum; Oxindoles; Physostigmine; Stereoisomerism

[reaction: see text] Starting from tryptamine 4 and isatin 5, a biomimetic approach to the pentacyclic substructure 1 of perophoramidine and communesin was developed. The key steps were to create a stable three/six bicyclic system 2 on the 2,3-double bond of an indole derivative 3 by an intramolecular cyclopropanation, followed by ring opening of the resulting cyclopropane ring with the in situ generated amine group of an aniline.

Topics: Cyclopropanes; Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Isatin; Molecular Mimicry; Molecular Structure; Tryptamines

Topics: Crystallography, X-Ray; Cyclization; Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Indoles; Models, Molecular; Molecular Structure; Sulfhydryl Compounds

An efficient synthetic strategy for installation of the two vicinal quaternary carbon centers of the communesins is reported. Key steps include the O-allylation/Claisen rearrangement of spirolactone systems, which are formed by tandem intramolecular Heck cyclization/carbonylation. Substituent and solvent effects on the stereochemical outcome of the Claisen rearrangements have been examined. The stereochemical assignment of the allyl spirolactone previously reported as 17 has now been revised to 31, which has the communesin relative configuration at the quaternary carbons. Key C-allyl spirolactone 59 bearing functional handles required for the communesin core has been constructed with a 9.8:1 diastereomer ratio.

Topics: Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Molecular Conformation; Stereoisomerism

The first total synthesis of racemic perophoramidine is described. The key step features the highly stereoselective introduction of the vicinial quaternary centers via base-promoted carbon-carbon bond formation between a 3-alkylindole and a 3-bromo-3-alkylindolin-2-one. This transformation presumably proceeds through a conjugate addition or Diels-Alder cycloaddition of the 3-alkylindole with a 3-alkylindol-2-one intermediate.

Topics: Cyclization; Heterocyclic Compounds, 4 or More Rings; Hydrocarbons, Halogenated; Lactones; Molecular Structure; Stereoisomerism