Total Synthesis of the Nagelamides - Synthetic Studies toward the Reported Structure of Nagelamide D and Nagelamide E Framework

The nagelamides are a small subset of the oroidin family of marine sponge-derived alkaloids and are, for the most part, dimeric in nature. As part of our efforts to develop synthetic access to this family, a Stille cross-coupling strategy is used to construct the bis-imidazolyl core skeleton. Reduct...

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Veröffentlicht in:Journal of organic chemistry 2020-10, Vol.85 (20), p.12971-12987
Hauptverfasser: Bhandari, Manojkumar R, Herath, Apsara K, Rasapalli, Sivappa, Yousufuddin, Muhammed, Lovely, Carl J
Format: Artikel
Sprache:eng
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Zusammenfassung:The nagelamides are a small subset of the oroidin family of marine sponge-derived alkaloids and are, for the most part, dimeric in nature. As part of our efforts to develop synthetic access to this family, a Stille cross-coupling strategy is used to construct the bis-imidazolyl core skeleton. Reduction of the bis-vinylimidazole delivered the core framework of nagelamide D. Introduction of the 2-amino groups via the corresponding azides and introduction of the pyrrolecarboxamides through a double Mitsunobu reaction using a pyrrole hydantoin provided the putative structure of nagelamide D. The spectroscopic data for the synthetic and sponge-derived materials did not match well, whereas the spectroscopic data were a good match for closely related oroidin alkaloids, supporting the structure of the synthetic material. The structure of the synthetic material was further corroborated by obtaining an X-ray crystal structure of a derivative. Electrocyclization of an advanced precursor affords a dihydrobenzimidazole, which is expected to serve as a key intermediate en route to nagelamide E and ageliferin.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.0c01617