The synthesis of emetine and related compounds. Part VI. Improvements in the synthesis of 3-alkyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxybenzo[a]quinolizin-2-ones and 3-alkyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-ones. Formation of some related diazabicyclo[3,3,1]nonanes

Selection of Evodiamine as a Novel Topoisomerase I Inhibitor by Structure-Based Virtual Screening and Hit Optimization of Evodiamine Derivatives as Antitumor Agents

“…The synthetic route of compounds 29a − x is depicted in Scheme . Evodiamine was synthesized by the reported procedure (Scheme ). − Starting from 24 , it was converted to amide 25 by reacting with ethyl formate. In the presence of POCl 3 , the key intermediate ABC ring 26 was obtained by ring closure reaction of amide 25 .…”

“…NaH (60% oil, 6.6 mmol) was suspended in a solution of evodiamine − (0.20 g, 0.66 mmol) in DMF (20 mL). The reacting mixture was heated to 80 °C and stirred for 24 h. The mixture was diluted with H 2 O (50 mL) and then extracted with EtOAc (50 mL × 3).…”

Synthetic Approaches to the New Drugs Approved During 2017

“…The key step in the synthesis of deutetrabenazine is the final transformation, which was achieved by reaction of 114 and quaternary ammonium salt 115 (whose preparation is outline in Scheme ) with K 2 CO 3 under heating conditions . This transformation presumably proceeded through a tandem Mannich reaction–Hofmann elimination–Michael addition sequence, which has been previously employed in the synthesis of tetrabenazine , and has also been reported successfully on kilogram scale with similar substrates . This cyclization sequence provided the racemic product as the cis-diastereomer , of deutetrabenazine ( XI ) in 67% yield after washing of the crude product with hot ethanol…”

Synthesis of (+)-Tacamonine via Stereoselective Radical Cyclization

“…To the best of our knowledge, the only prior work to employ such an ABC to the ABCDE strategy in the tacaman series was Padwa’s inventive carbonyl-ylide-based route to (±)- 1 , although Qin has recently published an AC to ABCD radical cyclization strategy for eburnane alkaloids . Specifically, we planned to leverage easily accessible 3,4-dihydro-β-carboline ( 14 ) as such an ABC fragment. Retrosynthetically, we therefore traced 1 back to a key ABCD tetracycle 12 , which we envisaged arising through a radical cyclization of tetrahydro-β-carboline 13 through the homolytic cleavage of its C-3 C–SPh bond and ensuing 6- exo-trig cyclization onto the pendant enoate ester group.…”

“…With gram quantities of 15 in hand, we explored its coupling to dihydro-β-carboline 14 (prepared in a one-pot process from tryptamine via a Bischler–Napieralski reaction) using our previously reported conditions . In the event, the treatment of a CH 2 Cl 2 solution of 15 with DCC, HOBt, and imine 14 , followed by cooling to −78 °C and the addition of PhSH and BF 3 ·OEt 2 , effected a net imine acylation/thiol trapping sequence to afford α-phenylsulfanyl amide 19 in 91% yield.…”