Synthetic studies of erythromycin derivatives: 6-O-methylation of (9S)-12,21-anhydro-9-dihydroerythromycin A derivatives |
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Authors: | Wei-Min ChenHenry NC Wong Daniel TW ChuXiaodong Lin |
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Institution: | a Department of Chemistry, Institute of Chinese Medicine and Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis,†1An Area of Excellence of the University Grants Committee (Hong Kong). The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People's Republic of China b Research and Development, Chiron Corporation, Emeryville, CA 94608-2916, USA |
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Abstract: | Synthetic studies on methylation of erythromycin derivatives were conducted. Methylation of 6 resulted in the formation of the C-3′ quaternary ammonium salts with a rate faster than 6-O-methylation. In dipolar aprotic solvent and under strong base conditions, 6-O-methylation, C-3′ quaternary ammonium salts formation and 2-C-methylation proceeded simultaneously to yield a mixture of three different products 7, 8 and 9. The quaternary ammonium salts were converted back to the corresponding tertiary amines 2, 10 and starting material 6 by employing sodium 4-pyridinethiolate as a N-demethylation reagent. The 6-O-methylation was eventually achieved in a good yield when a carbobenzyloxy (Cbz) group was utilized to protect the C-3′-dimethylamino group of 4. In this report, we will discuss the details of different reaction courses in the methylation of (9S)-12, 21-anhydro-9-dihydroerythromycin A derivatives. |
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Keywords: | (9S)-12 21-anhydro-9-dihydroerythromycin A modification 6-O-methylation N-demethylation |
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