- Trisoxazoline/Cu(II)-catalyzed asymmetric intramolecular Friedel-Crafts alkylation reaction of indoles
Intramolecular Friedel-Crafts alkylation reaction of indoles catalyzed by trisoxazoline/copper(II) is described. This annulation provides an easy access to polycyclic indole derivatives with up to 90% ee in up to 99% yield.
- Zhou, Jiao-Long,Ye, Meng-Chun,Sun, Xiu-Li,Tang, Yong
supporting information; experimental part
p. 6877 - 6881
(2009/12/06)
- A scalable process for the synthesis of the Bcl inhibitor obatoclax
Recently we created the novel indolylprodigiosin derivative 2 (obatodax) and demonstrated its ability to antagonize multiple members of the B-cell lymphoma (Bd) family of antiapoptotic proteins. The compound has shown potent anticancer activity in several animal tumor models. Obatodax is now in Phase 1b and 2 clinical trials directed against multiple hematologic and solid tumor malignancies. To support its clinical development, a new scalable synthesis was required. Obatodax has been prepared using a three-step synthesis, starting from commercially available 4-methoxy-3-pyrrolin-2-one. The reaction sequence involves a haloformylation reaction followed by a Suzuki cross-coupling reaction with an indole-2-boronic add. The synthesis is completed by an acid-mediated condensation with 2,4-dimethyl-1H-pyrrole.
- Dairi, Kenza,Yao, Yuxing,Faley, Michael,Tripathy, Sasmita,Rioux, Elise,Billot, Xavier,Rabouin, Daniel,Gonzalez, Gerson,Lavallee, Jean-Francois,Attardo, Giorgio
p. 1051 - 1054
(2012/12/30)
