Synthesis-driven mapping of the dictyodendrin alkaloids

A formal total synthesis of the telomerase inhibitor dictyodendrin B

“…Recently, Fürstner et al reported that dictyodendrin B (2), E (5) and even its desulfated derivative have ability to cleave double strand DNA under oxidative conditions. 2 The first total synthesis of dictyodendrin B (2) has been achieved by Fürstner's group in 2005. 3 They utilized a low-valent titanium-mediated reductive cyclization and subsequent photochemical dehydrogenative cyclization for formation of the core pyrrolo [2,3-c]carbazole ring.…”

“…Analysis of the 1 H NMR spectrum of the cyclized product confirmed that the reaction afforded only a single diastereomer, whose relative stereochemistry was identified as 4S * ,5R * on the basis of strong NOE correlation between 5-H and 2"'-H. A similar ring construction by a low-valent titanium-mediated oxo-ester coupling reaction has been reported for the synthesis of benzo[c]carbazole analogs of dictyodendrin. 2 However, a low-valent titanium (TiCl 4 /Zn) 12 and a magnesium (Mg, TMSCl) 13 reagents were not effective for the pinacol coupling of 7. An acidcatalyzed dehydration of 23 using CSA in CH 2 Cl 2 , which was accompanied by deprotection of the SEM ether, methylation of the resulting hydroxyl group, and debenzylation afforded an single product, however, its 1 H NMR spectrum data did not match with that of 6 reported by Fürstner et al 3 The compound thus obtained was identified to be the rearranged compound 27 on the basis of 1 H NMR spectrum (Figure 2), in which both methylenes of the phenethyl moiety of 27 ( H 3.09 and 4.67 ppm), which are out of the shielding cone of the adjacent aromatic ring, resonates 0.57-0.71 ppm downfield to those of 6 ( H 2.52 and 3.96 ppm).…”

Synthesis and Applications of Dihydropyrrolocarbazoles

“…Fürstner's group published the synthesis of dictyodendrin derivatives, performed via B ring closure by electrocyclization. [36] However, contrarily to what was presented above for the same research group, the starting material used to perform the cyclization was not a 2-vinyl-3-(pyrrol-3-yl)indole derivative but 2-acetylenyl-3-(pyrrol-3-yl)indole 122. Using electrophilic reagents such as (Ph 3 P)AuCl/AgSbF 6 or [I(pyridine) 2 ]BF 4 , compounds 123 and 124 were obtained, respectively (Scheme 21).…”

Synthetic Approach to Dictyodendrins: A Facile Synthesis of Pyrrolo[2,3‐c]carbazole, Pyrrolodibenzothiophene, and Benzo[e]indole

“…[6] Some of these synthetic dictyodendrin analogues [6] cleave double-stranded DNA under oxidative conditions. Fürstner and co-workers reported the synthesis of dictyodendrin-inspired natural product-like targets.…”