Diels-Alder reactivity of pyrano[3,4-b]indol-3-ones. Part 4. Synthesis of the carbazole alkaloids carbazomycin A and B and hyellazole

Abstract

The first synthesis of the carbazole alkaloids carbazomycins A and B (1) is described. The key step is the regioselective Diels-Alder reaction between 1 -methylpyrano [3,4-61 indol-3-one (4) and ethyl trimethylsilyl propynoate to give ethyl 1 -methyl-3-trimethylsilylcarbazole-2-carboxylate (6). The ester and trimethylsilyl groups in carbazole ( 6 ) are converted into methyl and methoxy groups respectively, and the final oxygen substituent is introduced, after protection of the carbazole nitrogen, by bromination, lithiation, formation of the corresponding borate, and oxidation. The carbazole alkaloid hyellazole (3a) is synthesised by a similar route from 1 -phenylpyrano[3,4-61 indol-3-one.The carbazomycins (l), isolated from Streptouertcillium, are the first antibiotics which contain the carbazole nucleus. The structure of carbazomycin B (1 b) was determined by extensive 'H and ' 3C n.m.r. studies, and was unequivocally confirmed to be 4-hydroxy-3-methoxy-1,2-dimethylcarbazole (1 b) by an Xray crystallographic analysis.2 Carbazomycin A was postulated to be 3,4-dimethoxy-1,2-dimethylcarbazole (la), by analogy with carbazomycin B, together with spectroscopic analysis, and chemical conversion of carbazomycin B into carbazomycin A with diazomethane. Carbazomycin B was found to be active against certain types of phytopathogenic fungi, and also showed rather weak antibacterial and anti-yeast activities. Carbazomycin A, however, showed only very weak antifungal and antibacterial activity." Since the isolation of carbazomycins A and B in 1980, another six members of the carbazomycin family, designated as carbazomycins C-H, have recently been isolated from the same Streptomjxes specie^.^ Y ( l a ) X = Y = OMe (carbazomycin A) (1 b ) X = OMe, Y = OH (carbazomycin B) (2a) X = H, Y = OMe (3-deoxycarbazomycin) (2b) X = OMe, Y = H (4-deoxycarbazomycin) xQJ--=-oMe Me

Biarylic Biscarbazole Alkaloids: Occurrence, Stereochemistry, Synthesis, and Bioactivity

“…The first oxidative dimerization24,25 of (unnatural) hydroxycarbazoles was found by serendipity, in the course of the synthesis of carbazomycins A ( 17 ) and B ( 18 ),26 which are antibiotic natural products from Streptoverticillium ehimense 27. Carbazomycin B ( 18 ) is the only carbazole for which extensive biogenetic experiments have been performed, leading to a far‐reaching understanding of its biosynthesis 5,28.…”

“…Carbazomycin B ( 18 ) is the only carbazole for which extensive biogenetic experiments have been performed, leading to a far‐reaching understanding of its biosynthesis 5,28. In an attempt to oxidize 3‐hydroxycarbazole 15 to the ortho‐quinone structure 16 by using dibenzoyl peroxide, Moody et al26 obtained the 4,4′‐dimer 19 in high yields (Fig. 3).…”

Enantioselective Vanadium-Catalyzed Oxidative Coupling: Development and Mechanistic Insights

“…Benzoyl peroxide was utilized by Moody and coworkers to make biscarbazole in 1989. 18 Bringmann and other groups used tert -butyl peroxide to oxidatively introduce the C-C bond from 1-hydroxycarbazoles. 19 Later, Knӧlker reported that tetrachloro- para -benzoquinone produced an axial bond ortho to the hydroxyl group.…”

Cycloadditions, Cycloisomerizations and Related Reactions of Alkynes Bearing Group 13 or 14 Heteroelements

“…(11). (33) was formed and reacted with another alkyne unit (34) to give arylboronate (35). It was subject, without purification, to the Suzuki-Miyaura coupling with aryl iodide (36) in aqueous toluene to afford biaryl compound (37).…”

“…(17). with electron-deficient dienes such as tetrazines [34] or pyranolones [35]. On the other hand, with electron-rich dienes, the DA reaction requires a stronger electronwithdrawing group on the alkyne, such as in MeO 2 CC CSnBu 3 [36].…”