The synthesis and antimicrobial activity heterocyclic analogs of the diterpenoid totarol are described. An advanced synthetic intermediate with a ketone on the A-ring is used to attach fused heterocycles and a carbon-to-nitrogen atom replacement is made on the B-ring by de novo synthesis. A-ring analogs with an indole attached exhibit, for the first time, enhanced antimicrobial activity relative to the parent natural product. Preliminary experiments demonstrate that the indole analogs do not target the bacterial cell division protein FtsZ as had been hypothesized for totarol.
The synthesis and antimicrobial activity heterocyclic analogs of the diterpenoid totarol are described. An advanced synthetic intermediate with a n class="Chemical">ketone on the A-ring is used to attach fused heterocycles and a carbon-to-nitrogen atom replacement is made on the B-ring by de novo synthesis. A-ring analogs with an indole attached exhibit, for the first time, enhanced antimicrobial activity relative to the parent natural product. Preliminary experiments demonstrate that the indole analogs do not target the bacterial cell division protein FtsZ as had been hypothesized for totarol.
Authors: Christopher M Tan; Alex G Therien; Jun Lu; Sang H Lee; Alexandre Caron; Charles J Gill; Christian Lebeau-Jacob; Liliana Benton-Perdomo; João M Monteiro; Pedro M Pereira; Nathaniel L Elsen; Jin Wu; Kathleen Deschamps; Mihai Petcu; Simon Wong; Etienne Daigneault; Susanne Kramer; Lianzhu Liang; Eugene Maxwell; David Claveau; John Vaillancourt; Kathryn Skorey; John Tam; Hao Wang; Timothy C Meredith; Susan Sillaots; Lisa Wang-Jarantow; Yeeman Ramtohul; Eric Langlois; France Landry; John C Reid; Gopal Parthasarathy; Sujata Sharma; Anastasia Baryshnikova; Kevin J Lumb; Mariana G Pinho; Stephen M Soisson; Terry Roemer Journal: Sci Transl Med Date: 2012-03-21 Impact factor: 17.956