Carbazoquinocin A

[reaction: see text] The photoinduced o-benzannulation of 3-(2-vinyl)indolylcarbene complexes provides a direct route to carbazole derivatives that are oxygenated in the 3- and 4-positions. This reaction is quite efficient and provides for a unique synthesis of the lipid peroxidation inhibitor carbazoquinocin C.

Development of an acid catalyzed, intramolecular benzannulation of indoles for the synthesis of functionalized carbazoles has been reported. The indole appended Z-enoate propargylic alcohols have been employed. The N-EDG-indoles involve the 5-exo-dig cyclization followed by 1,2-migration to give the carbazole-butenoates, whereas the N-EWG-indoles undergo the Z-enoate assisted Meyer-Schuster rearrangement to give the dihydrocarbazole-4-oxo-butanoates. Utilizing one of the 2-methyl-carbazole-butyraldehyde (obtained from the corresponding carbazole-butanoate) as the key intermediate, we have developed a simple approach for an efficient synthesis of N-Me-carazostatin, N-Me-carbazoquinocin C and N-Me-lipocarbazole A4.

Co-cultivation has been used as a promising tool to turn on or up-regulate cryptic biosynthetic pathways for microbial natural product discovery. Recently, a modified culturing strategy similar to co-cultivation was investigated, where heat-killed inducer cultures were supplemented to the culture medium of producer fermentations to induce cryptic pathways. In the present study, the repeatability and effectiveness of both methods in turning on cryptic biosynthetic pathways were unbiasedly assessed using UHPLC-HRESIMS-based metabolomics analysis. Both induction methods had good repeatability, and they resulted in very different induced metabolites from the tested producers. Co-cultivation generated more induced mass features than the heat-killed inducer cultures, while both methods resulted in the induction of mass features not observed using the other induction method. As examples, pathways leading to two new natural products, N-carbamoyl-2-hydroxy-3-methoxybenzamide (1) and carbazoquinocin G (5), were induced and up-regulated through co-culturing a producer Streptomyces sp. RKND-216 with inducers Alteromonas sp. RKMC-009 and M. smegmatis ATCC 120515, respectively.