O-Methylation effect on the carbon-13 nuclear magnetic resonance signals of ortho-disubstituted phenols and its application to structure determination of new phthalides from Aspergillus silvaticus.

Abstract

The O-methylation effect on the carbon-13 nuclear magnetic resonance chemical shifts of ortho-disubstituted phenols was investigated. In phenols with nonconjugated ortho-disubstituents (1-10), O-methylation caused a downfield shift by an average of 5.2 ppm for the ortho-carbons (C-2 and -6), and a downfield shift by an average of 4.6 ppm for the para-carbon (C-4). These shift values are significantly different from those observed in ortho-monosubstituted and ortho-nonsubstituted phenols. This regularity is very useful for the spectral interpretation of some natural products with an ortho-disubstituted phenol group and for the determination of the position of the methoxy group in such compounds. Two new phthalides, silvaticol (15) and O-methylsilvaticol (16), were isolated along with nidulol (17) from Aspergillus silvaticus. In the course of the structure determination of these compounds, the O-methylation effects of ortho-mono-and ortho-disubstituted phenols were successfully applied to these phthalides. The structures of silvaticol and O-methylsilvaticol were determined as 6-hydroxy-4-methoxy-5-methylphthalide and 4, 6-dimethoxy-5-methylphthalide, respectively.