Studies on quinones. Part 21. Regioselective synthesis of tetracyclic quinones related to rabelomycin

Angucyclines: Total syntheses, new structures, and biosynthetic studies of an emerging new class of antibiotics

“…The authors also observed base-catalyzed air oxidation to the ketone 53, analogous to similar oxidations of benzylic carbanions (compare with [56] 15. Diels-Alder reaction using ketene acetal 51 and base-catalyzed air oxidation at C-1 [47] 138 K. Krohn-l. Rohr The benzo[a]anthraquinone skeleton 56 was also formed in an interesting rearrangement of a spirodienone 55 prepared by Diels-Alder reaction of butadiene with the spirooquinone 54 [57].…”

“…The carbonyl group at C-1 was introduced by a series of steps including selenohydroxylation and chromium(VI) oxidation followed by radical deselenation. Easier solutions such as the photooxygenation (see Scheme 8) or the basecatalyzed oxygenations for 3-deoxyangucyclinones [47] were later developed for introduction of the oxygen at C-1 (vide infra). The final demethylation of X-14881C (34) to the phenolic ochromycinone (35) using aluminum trichloride proceeded without problems (Scheme 9).…”

“…As shown in Scheme 2, elimination of the tertiary hydrox y group of tetrangomycin (2) to form tetrangulol (3) is no problem. In the absence of this hydroxy group, conversion of ochromycinone (35) [54] In related investigations Valderrama et al [47] studied the reaction of naphthoquinone (40) and juglone (47) with the ketene acetal 51. Using this oxidation state, the oxygen substituent in the product is always preserved at the terminal position of dienes (compare anthracycline chemistry [55]).…”

“…A kinetic resolution with respect to the racemic diene 66 could be achieved in the Diels-Alder reaction promoted by a chiral Lewis acid prepared from BH 3 in the presence of (S)-3,3"-diphenyl-l,l"-binaphthalene-2,2"-diol and juglone (47) in the synthesis of (+)-emycin A and (+)-ochromycinone (35) [66] (compare previous investigations by Kelly [67] In our group, we focused on the possible introduction of the labile hydroxy group at C-3. Keeping in mind that the C-1 carbonyl oxygen can be introduced at a later stage by photooxygenation under neutral conditions (see Scheme 8), juglone (47) and the diene 70 resulted from the retrosynthetic analysis of the Diels-Alder route to rabelomycin (29).…”

“…Keeping in mind that the C-1 carbonyl oxygen can be introduced at a later stage by photooxygenation under neutral conditions (see Scheme 8), juglone (47) and the diene 70 resulted from the retrosynthetic analysis of the Diels-Alder route to rabelomycin (29). We presumed that the required diene building block 70 would be relatively unstable and difficult to prepare.…”