Synthesis and cytotoxicity studies of achiral azaindole-substituted titanocenes

✍ Scribed by Luis Miguel Menéndez Méndez; Anthony Deally; Donal F. O'Shea; Matthias Tacke

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 273 KB
• Volume: 22
• Category: Article
• ISSN: 1042-7163
• DOI: 10.1002/hc.20668

✦ Synopsis

Abstract

From the reaction of 1‐methyl‐1 H‐pyr‐rolo[2,3‐b]pyridine (1a),1‐(methoxymethyl)‐1 H‐pyrrolo[2,3‐b]pyridine (1b), 1‐isopropyl‐1 H‐pyrrolo[2,3‐b]pyridine (1c), and 1‐(4‐methoxybenzyl)‐1 H‐pyrrolo[2,3‐b]pyridine (1d) under Vilsmeier–Haak conditions, the corresponding aldehydes in position 3 (2a–2d) were synthesized. These aldehydes were transformed in the corresponding fulvenes (3a–3d) by the Knoevenagel condensation and treated with Li[BEt~3~H] to obtain the corresponding lithiated cyclopentadienide intermediates (3′a–3′d). These intermediates were, finally transmetallated to titanium with TiCl~4~ to yield the 7‐azaindol‐3‐yl‐substituted titanocenes bis {[(1‐methyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl] cyclopentadienyl} titanium(IV) dichloride (4a), bis{[(1‐methoxymethyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV)dichloride (4b), bis{[(1‐Isopropyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV) dichloride (4c), and bis{[(4‐methoxybenzyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV) dichloride (4d). All the titanocenes had their cytotoxicity investigated through MTT‐based preliminary in vitro testing on the Caki‐1 cell lines to determinate their IC~50~ values. Titanocenes 4a–4c were found to have IC~50~ values of 120 ± 10, 83 ± 13, and 54 ± 12, µM respectively, whereas 4d showed no cytotoxic activity. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:148–157, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20668