A novel total synthesis of the bioactive poly-substituted carbazole alkaloid carbazomadurin A

Total Synthesis of the Neuronal Cell‐Protecting Carbazole Alkaloids Carbazomadurin A and (S)‐(+)‐Carbazomadurin B

“…On the other hand, the cross‐coupling reaction of the triflate 21 with 3a or 3b in the presence of Na 2 CO 3 and Pd(PPh 3 ) 4 gave the corresponding 1‐alkenylcarbazoles 25a (86 %) and 25b (83 %, [ α ] D = +7.1), respectively. Although reduction of the formyl group of 25a afforded alcohol 26 , the sequential treatment with TBAF did not provide carbazomadurin A ( 1a ) as had been previously reported 12. As a result, the cleavage of both SEM groups of 25a and 25b by using TBAF in hexamethylphosphoramide (HMPA) produced the expected 3,8‐dihydroxycarbazole 27a (71 %) and 27b (67 %, [ α ] D = +20.0), respectively.…”

“…The Grignard reaction of 13a and 13b with ethynylmagnesium bromide followed by treatment of the resulting alcohols 14a and 14b with MOMCl and i Pr 2 NEt produced MOM propargyl ethers 15a ( E / Z , 1:3) and 15b ( E / Z , 1:3) corresponding to 5 . We subjected 15a and 15b to an allene‐mediated thermal electrocyclic reaction6–12 using tetra‐ n ‐butylammonium fluoride (TBAF) in tetrahydrofuran (THF) according to our reported method8b to provide the desired carbazoles 16a and 16b corresponding to 2 , respectively, in somewhat low yields. The oxidation of 16a and 16b with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) afforded 5‐formylcarbazoles 17a and 17b , which were treated with 4 M HCl in THF to yield the 1‐hydroxycarbazoles 18a and 18b .…”

“…Among these, we have reported the total syntheses of the hyellazoles, carazostatin, the carbazoquinocins,7 murrayaquinone, furocarbazole, carbazomycin G,8 the calothrixins,9 mukonine,10 and the carquinostatins11 by using an allene‐mediated thermal electrocyclic reaction that involves the indole 2,3‐bond. Recently, we reported a new total synthesis of carbazomadurin A ( 1a ) by using our methodology through the construction of a highly substituted carbazole framework 12. Herein, we describe the detailed total synthesis of carbazomadurin A ( 1a ) and a new asymmetric total synthesis of ( S )‐(+)‐carbazomadurin B ( 1b ).…”

Recent Applications of Phosphane-based Palladium Catalysts in Suzuki-Miyaura Reactions Involved in Total Syntheses of Natural Products

“…[108] In 2010, Choshi, Hibino and co-workers described a total synthesis of the neuronal cell protecting carbazole alkaloid carbazomadurin A (33) in which the (E)-alkenyl side chain at the C1 position of carbazole was introduced by the Pd(PPh3)4-catalyzed reaction of pinacol boronate A27 with triflate B30 (entry 31, Table 2). [109] Unfortunately, the detailed experimental conditions of the coupling, which was carried out in DMF using Na2CO3 as base to provided compound C27 in almost quantitative yield, were not In 2012, Fürstner and co-workers reported the first total synthesis of the structurally challenging and biologically highly promising antimitotic agent leiodermatolide (34). [110] Compound C28, an advanced intermediate to 34, was synthesized in 56% yield by the Pd(PPh3)4-catalyzed reaction of boronate A28 with vinyl iodide B31 (entry 32, Table 2).…”

Total Synthesis of (&plusmn;)-Carquinostatin A, and Asymmetric Total Synthesis of (<i>R</i>)-(−)-Carquinostatin A and (<i>S</i>)-(+)-Carquinostatin A

“…18,19) To synthesize the highly functionalized carbazole alkaloid, we have constructed a carbazole framework based on an allenemediated electrocyclic reaction with a tautomeric process involving the indole 2,3-bond. [20][21][22][23][24][25][26][27][28][29][30] In 2007, we reported the lipase-QLM catalyzed enantioselective synthesis of (R)-(−)-6-desprenylcarquinostatin and its (S)-(+)-enantiomer from 1-acetonyl-3-ethoxy-2-methylethoxycarbazole (5) (Fig. 1), which was prepared using an allene-mediated electrocyclic reaction.…”