title: Total synthesis and cytotoxic activity of stellatin.
abstract: Stellatin (3,4-dihydro-8-hydroxy-7-hydroxymethyl-6-methoxyisocoumarin) (8), an extrolite of fungal genera Emericella and Aspergillus, was synthesized. Thus, Vilsmeier-Haack formylation of methyl ester of 3,5-dimethoxy-4-methylphenylacetic acid (1) to afford the formyl ester (2) followed sulfamic acid-sodium chlorite oxidation of the aldehydic function to yield the carboxy ester (3). Chemoselective reduction of ester function in the latter using NaBH(4)/THF/MeOH furnished the corresponding hydroxy acid (4) that on cyclodehydration afforded the 3,4-dihydro-6,8-dimethoxy-7-methylisocoumarin (5). Benzylic bromination of the C-7 methyl in 5 using NBS/benzoyl peroxide to give the 7-bromomethyldihydroisocoumarin (6) followed the nucleophilic substitution using aqueous acetone to provide 7-hydroxymethyl-dihydroisocoumarin (7). Finally, the regioselective demethylation of 8-methoxyl group using anhydrous magnesium iodide furnished the stellatin (8). The dihydroisocoumarins (5-8) were screened for cytotoxic activity against human keratinocyte cell line and were found to exhibit moderate to good activity.
authors.affiliation: Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan. aamersaeed@yahoo.com
authors.forename: Aamer
authors.initials: A
authors.lastname: Saeed
authors.forename: Zaman
authors.initials: Z
authors.lastname: Ashraf
authors.forename: Hummera
authors.initials: H
authors.lastname: Rafique
mesh_terms: D001230:Aspergillus / Q000737:chemistry; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D032842:Emericella / Q000737:chemistry; D006801:Humans; D049934:Isocoumarins; D015603:Keratinocytes / Q000187:drug effects; D015394:Molecular Structure
chemical_list: D003374:Coumarins; D003603:Cytotoxins; D049934:Isocoumarins; C556133:stellatin