864816-22-8Relevant articles and documents
Total syntheses of the telomerase inhibitors dictyodendrin B, C, and E
Fuerstner, Alois,Domostoj, Mathias M.,Scheiper, Bodo
, p. 8087 - 8094 (2007/10/03)
Concise and flexible total syntheses of the pyrrolo[2,3-c]carbazole alkaloids dictyodendrin B (2), C (3), and E (5) are described. These polycyclic telomerase inhibitors of marine origin derive from the common intermediate 18 which was prepared on a multigram scale by a sequence comprising a TosMIC cycloaddition with formation of the pyrrole A-ring, a titanium-induced reductive oxoamide coupling reaction to generate an adjacent indole nucleus, and a photochemical 6π-electrocyclization/aromatization tandem to forge the pyrrolocarbazole core. Conversion of 18 into dictyodendrin C required selective manipulations of the lateral protecting groups and oxidation with peroxoimidic acid to form the vinylogous benzoquinone core of the target. Zinc-induced reductive cleavage of the trichloroethyl sulfate ester then completed the first total synthesis of 3. Its relatives 2 and 5 also originate from compound 18 by a selective bromination of the pyrrole entity followed by elaboration of the resulting bromide 27 via metal-halogen exchange or cross-coupling chemistry, respectively. Particularly noteworthy in this context is the generation of the very labile p-quinomethide motif of dictyodendrin E by a palladium-catalyzed benzyl cross-coupling reaction followed by vinylogous oxidation of the resulting product 41 with DDQ. The Suzuki step could only be achieved with the aid of the borate complex 40 formed in situ from p-methoxybenzylmagnesium chloride and 9-MeO-9-BBN, whereas alternative methods employing benzylic boronates, -trifluoroborates, or -stannanes met with failure.
Total synthesis of dictyodendrin B
Fuerstner, Alois,Domostoj, Mathias M.,Scheiper, Bodo
, p. 11620 - 11621 (2007/10/03)
A concise total synthesis of dictyodendrin B (1) is reported, a scarce marine alkaloid endowed with promising telomerase inhibitory activity. Key steps of the chosen route are a reductive cyclization of ketoamide 11 to indole 12 mediated by low-valent titanium (from TiCl3 and KC8) followed by a photochemical 6π-electrocyclization, which was performed in the presence of Pd/C and nitrobenzene to effect concomitant dehydrogenation/aromatization of the product initially formed. Regioselective bromination of the resulting pyrrolocarbazole 13 followed by lithium/bromine exchange and quenching of the resulting organolithium species with p-methoxybenzaldehyde installed the side chain at C2. Oxidation of the benzylic alcohol 15 thus obtained to ketone 17 was best achieved with catalytic amounts of tetra-n-propylammonium perruthenate (TPAP) and N-methylmorpholine-N-oxide (NMO) in dilute CH2Cl2 solution to avoid the formation of undue amounts of the unsymmetrical dimer 16. Ketone 17 was elaborated into the natural product by selective cleavage of the isopropyl ether with BCl3, introduction of the sulfate moiety with the aid of trichloroethyl chlorosulfuric acid ester, deprotection of all lateral methyl ether groups, and final reductive cleavage of the trichloroethyl ester moiety. The spectroscopic data of synthetic dictyodendrin B thus formed matched those of an authentic sample in all regards. Moreover, it was shown that global deprotection of the peripheral -OH groups in pyrrolo[2,3-c]carbazole 13 is accompanied by spontaneous air-oxidation to form the quinone core of dictyodendrin C. Copyright
