A concise synthesis of the Lycopodium alkaloid cermizine D

Abstract

Please cite this article as: Enamorado, M.F., Connelly, C.M., Deiters, A., Comins, D.L., A concise synthesis of the Lycopodium alkaloid cermizine D, Tetrahedron Letters (2015), doi: http://dx.ABSTRACT: A racemic and asymmetric synthesis of cermizine D (1) was accomplished in six steps from 4-methoxypyridine or 4-methoxy-3-TIPS-pyridine in 12% and 13% overall yield, respectively. A key step is a stereoselective 1,4-addition of a 2-((trimethylsilyl)methyl)pyridine-derived cuprate to a bicyclic 2,3-dihydro-4-pyridone. Racemic and (-)-cermizine D failed to exhibit cytotoxicity against four different cell lines.

A Practical Total Synthesis of (±)-Cermizine D and a Formal Synthesis of (±)-Cermizine C

“…24 Recently, Comins and co-workers reported a sixstep total synthesis of (-)-cermizine D through an asymmetric nucleophilic addition of a pyridinium salt. 25 In the present study, (±)-cermizines C and D were prepared effectively using 2-picoline in five and four steps, respectively (Fig. 1).…”

“…1). [5][6][7][8][9][10][11][12] Although cermizine C has been the topic of numerous synthetic papers, 7,8,[13][14][15][16][17][18][19][20][21][22] to date there have been only three total syntheses of cermizine D. 20,[23][24][25] In 2008, Takayama and co-workers reported the first asymmetric total synthesis of (+)cermizine D, which consisted of an 18-step route featuring an oxazolidinone intermediate as a key cyclisation precursor. 20,23 In 2012, a second synthesis of (+)-cermizine D was published by Carter and collaborators, which included two different approaches, a nine-step cuprate addition strategy and a PhSCH 2 I alkylation pathway in 16 steps overall.…”

Synthesis of quinolizidine-containing lycopodium alkaloids and related natural products

“…17 Lasubines I (2.5) and II (2.6) were isolated from lagerstroemia M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 8 of the more complicated members cernuine (2.8) 20 and cermizine D (2.7). 20,21,22 This quinolizidine scaffold is also present in other complex members of the lycopodium alkaloids such as himeradine A (1.6). 23 Our interest in the quinolizidine scaffolds has also included our synthetic studies toward himeradine A and thus expanded into developing general approaches to access significant cross sections of the lycopodium alkaloid family.…”

Synthesis of 1-Amino-2H-quinolizin-2-one Scaffolds by Tandem Silver Catalysis

“…Meanwhile, quinolizidine derivatives are also the indispensable frameworks of numerous natural products, as shown in Figure . Inspired by their intriguing structures and biological significance, the construction of quinolizidine frameworks has propagated much research effort to develop novel and efficient methodologies …”