Synthesis of isoquinolines and tetrahydroisoquinolines as potential antitumour agents

An interesting sidetrack in the tofisopam synthesis: lithium variant of a stereospecific Oppenauer oxidation

“…4 equivalent of 3,4,5-trimethoxybenzaldehyde gave benzophenone 15 in 71% yield (Scheme 4). 18 The authors remarked that attempts to isolate alcohol 16 failed due to the fast oxidation of the lithium salt of 16 to ketone 15, however, they did not comment on the mechanism of this unique lithium-catalyzed Oppenauer oxidation. …”

Synthesis of Nine Safrole Derivatives and Their Antiproliferative Activity Towards Human Cancer Cells

“…Safrole, from sassafras oil (Ocotea pretiosa Mez., Lauraceae), is an abundant natural product showing interesting functionality and chemical structure. The methylenedioxy unit, present in safrole, can be identified in the clinical antitumour agents etoposide and teniposide 1 and lignan lactone podophylotoxin 2 . We have shown what eugenol and this derivates present antioxidant capacity evaluated by the DPPH (1,1-diphenyl-2-picrylhydrazil) and ORAC assays.…”

“…Safrole (1) and its synthetic derivatives (2)(3)(4)(5)(6)(7)(8) were tested in vitro for antiproliferative effect on two human tumor breast cancer cell lines (MDA-MB-231, MCF-7), one human colorectal cancer cell line (DLD-1) and one dermal human fibroblast cell line (DHF). The in vitro growth inhibition assay used was based on sulphorhodamine dye, widely used to quantify cell viability.…”

Synthesis and Biological Evaluation of Novel Compounds Related to 1-Arylnaphthalene Lignans and Isoquinolines

“…Under the Schotten ± Baumann conditions, these amines were condensed with two kinds of trisubstituted benzoyl chlorides 15 and 16 to afford the expected N-(2-phenylethyl)benzamides 17 ± 23. The cyclization of the amides to PhDHIQs 30 ± 34 was accomplished with POCl 3 by Bischler ± Napieralski reaction [10]. However, to our surprise, not all cyclizations could be accomplished to give the expected 3,4-dihydroisoquinolines.…”

“…The reaction was found to depend on the substituents on the phenyl ring of the 2-phenylethyl moiety, since 4-MeO-and 4-BnO-substituted amides failed to cyclize. The prepared PhDHIQs were subjected to dehydrogenation in the presence of Pd/C to furnish the corresponding isoquinolines PhIQs 37 ± 41 (Scheme 1 and Table 1) [10].…”