Chemical aromatization of 19-hydroxyandrosta-1,4-diene-3,17-dione with acid or alkaline: Elimination of the 19-hydroxymethyl group as formaldehyde |
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Authors: | Mitsuteru Numazawa Kouwa Yamashita Nao Kimura Madoka Takahashi |
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Institution: | Tohoku Pharmaceutical University, 1-4 Komatsushima-4-chome, Sendai 981-8558, Japan |
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Abstract: | In order to determine whether or not a 19-hydroxymethyl group of 19-hydroxyandrosta-1,4-diene-3,17-dione (2, 19-hydroxy ADD), an intermediate of aromatase-catalyzed estrone formation from ADD, a suicide substrate of aromatase, is eliminated as formaldehyde, we examine chemical nature of removal of the 19-hydroxymethyl group. 19-Acetate 3 and 19-tert-butyldimethylsiloxy compound 4 are known to convert rapidly to estrone with treatment of NaOH or n-Bu4NF. Since compound 2 was unstable and unobtainable under these conditions, compounds 3 and 4 as equivalents to compound 2 were used in this study. The acetate 3 with 5 mol/l HCl in acetone and 10% KOH in MeOH along with the silyl ether 4 with 5 mol/l HCl in acetone and 1 mol/l n-Bu4NF in THF gave formaldehyde and estrone in which a ratio of the aldehyde to estrone was near 1. This result indicates that the 19-hydroxymethyl groups of compound 3 and 4 are eliminated as formaldehyde along with estrone derived from the steroid skeleton under the acid or base treatment. The findings suggest that a single hydroxylation at the 19 carbon of ADD (1) would be, chemically, all that was required for estrone formation. |
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Keywords: | 19-Hydroxyandrosta-1 4-diene-3 17-dione Chemical aromatization Formaldehyde formation Acid-catalyzed reaction Base-catalyzed reaction |
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