Chemical aromatization of 19-hydroxyandrosta-1,4-diene-3,17-dione with acid or alkaline: elimination of the 19-hydroxymethyl group as formaldehyde.
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.
Numazawa
Mitsuteru
M
Tohoku Pharmaceutical University, 1-4 Komatsushima-4-chome, Sendai 981-8558, Japan. numazawa@tohoku-pharm.ac.jp
Yamashita
Kouwa
K
Kimura
Nao
N
Takahashi
Madoka
M
D000085:Acetates / Q000737:chemistry; D000096:Acetone / Q000737:chemistry; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000737:chemistry; D004970:Estrone / Q000737:chemistry; D004987:Ethers / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration
C539865:19-hydroxyandrosta-1,4-diene-3,17-dione; D000085:Acetates; D004987:Ethers; D000096:Acetone; D005557:Formaldehyde; D004970:Estrone; D000735:Androstenedione