Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine

Trost, Barry M.; Osipov, Maksim

doi:10.1002/chem.201501735

Cited by 86 publications

(23 citation statements)

References 77 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perophoramidine ( 2 ) has demonstrated activity against the HCT116 colon carcinoma cell line with an IC 50 of 60 μm, while communesin F ( 3 ) was shown to exhibit insecticidal activity against instar silkworm's larvae. Because of their intriguing structures and promising biological activities, this family of alkaloids has stimulated substantial interest from the scientific community and has resulted in a number of elegant syntheses …”

Section: Figurementioning

confidence: 99%

Concise Total Synthesis of Dehaloperophoramidine

2015

View full text Add to dashboard Cite

Perophoramidine, dehaloperophoramidine, and communesin F are structurally related alkaloids having intriguing polycyclic structures. A strategy for the synthesis of dehaloperophoramidine has been developed. In this synthesis all skeletal atoms and all functional groups required to reach the target molecule are incorporated early in the sequence. This approach led to the discovery of two novel substrate-specific domino processes, one encompassing four steps and the other comprising five steps, thus resulting in an eight-step synthesis of dehaloperophoramidine.

show abstract

Section: Figurementioning

confidence: 99%

Concise Total Synthesis of Dehaloperophoramidine

2015

View full text Add to dashboard Cite

show abstract

“…1 The core structures of these alkaloids feature seven contiguous rings, two aminal linkages, and up to six stereogenic centers, of which two are vicinal and quaternary (C3a/C3a′). This formidable structural complexity coupled with an array of important biological activity prompted research efforts directed toward their total chemical synthesis, culminating in inventive solutions for the preparation of racemic 2 and enantiomerically enriched 3 samples of communesin F ( 1 ). However, access to the more complex C10-epoxide-containing communesins remains challenging.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives

2019

View full text Add to dashboard Cite

A unified enantioselective total synthesis and anticancer evaluation of all known epoxide-containing communesin alkaloids and related derivatives is described. Our synthesis is predicated on the convergent and modular diazene-directed assembly of two complex fragments to secure the critical C3a–C3a′ linkage followed by a guided biomimetic aminal reorganization to deliver the heptacyclic core of these alkaloids. Concise enantioselective syntheses of the fragments were devised, with highlights including the application of a rationally designed sulfinamide chiral auxiliary, an efficient calcium trifluoromethanesulfonate promoted intramolecular amination, and a diastereoselective epoxidation that simultaneously converts the new chiral auxiliary to a versatile amine protective group. The modularity of our convergent approach enabled the rapid synthesis of all epoxide-containing members of the communesin family from a single heterodimeric intermediate, including the first total synthesis of communesins C–E, and G–I, and facilitated our stereochemical revision of (−)-communesin I, the most recently isolated communesin alkaloid. Furthermore, the generality of our biogenetically inspired heterodimer rearrangement was demonstrated in a guided synthesis of a communesin derivative with an unnatural topology. Finally, we report the first comparative analysis of the anticancer activities of all naturally occurring communesin alkaloids A–I and eight complex derivatives against five human cancer cell lines. From these data, we have identified (−)-communesin B as the most potent natural communesin and discovered that derivatives with N8′-sulfonamide substitution exhibit up to a 10-fold increase in potency over the natural alkaloids.

show abstract

“…Because of their unique structure and biological activity, many research groups have conducted synthetic studies of communesins in which various synthetic methods were developed. [9][10][11][12][13][14] The first racemic total synthesis of communesin F was achieved by Qin and co-workers based on an intramolecular cyclopropanation strategy. 15 Weinreb and Funk also reported total synthesis of communesin F, independently.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the ABCDG ring skeleton of communesin F based on carboborylation of 1,3-diene and Bi(OTf)3-catalyzed cyclizations

et al. 2019

View full text Add to dashboard Cite

Communesins, isolated from the mycelium of a strain of Penicillium sp., are cytotoxic heptacyclic indole alkaloids bearing a bis-aminal structure and two contiguous quaternary carbon centers. Towards a total synthesis of communesin F, we synthesized a pentacyclic ABCDG ring skeleton via carboborylation of 1,3-diene and a Friedel-Crafts-type cyclization, resulting in the formation of an azepine ring through a Bi(OTf)3-catalyzed SN2' reaction.

show abstract

Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine

Cited by 86 publications

References 77 publications

Concise Total Synthesis of Dehaloperophoramidine

Concise Total Synthesis of Dehaloperophoramidine

Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives

Synthesis of the ABCDG ring skeleton of communesin F based on carboborylation of 1,3-diene and Bi(OTf)3-catalyzed cyclizations

Contact Info

Product

Resources

About