Sterically Congested Adamantylnaphthalene Quinone Methides

Abstract

Five new (2-adamantyl)naphthol derivatives (5-9, quinone methide precursors, QMP) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of QMP 5 to S(1) leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide QM5 which was characterized by LFP (in CH(3)CN-H(2)O, λ(max) = 370 nm, τ = 0.19 ms). On irradiation of QMP 5 in CH(3)OH-H(2)O (4:1), the quantum yield of methanolysis is Φ = 0.70. Excitation of naphthols QMP 6-8 to S(1) in CH(3)CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, QMP 6-8 undergo solvent-assisted PT giving QM6 or zwitterion QM8 that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. QMP 9 in a protic solvent undergoes two competitive processes, photosolvolysis via QM9 and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. QM9 has been characterized by LFP (in CH(3)CN-H(2)O, λ(max) > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, QM10 and QM11 were synthesized thermally and characterized by X-ray crystallography. QM10 and QM11 do not react with H(2)O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of 5-9 was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with 5 to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of QM5.

In vitro investigation of the antimicrobial activity of a series of lipophilic phenols and naphthols

“…23 Characterization of product 36 compares well with literature (mp = 250-252°C). 23 2-(2-Amino-2-adamantyl)-6-hydroxynaphthalene hydrochloride (37) was obtained from 2-(2-azido-2-adamantyl)-6-hydroxynaphthalene by reduction with Raney Ni in 19 % yield according to the published procedure. 23 Characterization of product 37 compares well with literature (mp = 256-258°C).…”

“…All compounds were prepared according to previously published procedures. [19][20][21][22][23] Chiral compounds 7-9 were synthesized as racemic mixtures.…”

“…21 Characterization of product 22 compares well with literature (mp = 125-130°C). (23) was prepared from 22 by treatment with sodium thiolate in 69 % yield according to the published procedure. 21 Characterization of product 23 compares well with literature (mp = 160-163°C).…”

“…23 2-(2-Amino-2-adamantyl)-6-hydroxynaphthalene hydrochloride (37) was obtained from 2-(2-azido-2-adamantyl)-6-hydroxynaphthalene by reduction with Raney Ni in 19 % yield according to the published procedure. 23 Characterization of product 37 compares well with literature (mp = 256-258°C). 1-(2-Hydroxy-2-adamantyl)-4-methoxynaphthalene (38) was prepared in a Grignard reaction from 1-bromo-4-methoxynaphthalene and 2-adamantanone in 68 % yield according to the published procedure.…”

“…18 We became interested in the photochemical generation of QMs with sterically congested lipophylic substituents 19,20 and their antiproliferative activities. [21][22][23][24] A series of simple phenols, 19 biphenyls, [20][21][22] naphthols, 23 and anthrols 24 were synthesized and their antiproliferative activities were investigated. Since compounds that generate QMs are known b-lactamase inhibitors, 18 we were also prompted to investigate their antimicrobic activities.…”