TY  - JOUR
PY  - 1993//
TI  - 1,4-addition reaction with thiols and conformational analysis with PM3 molecular orbital calculations of 19-oxygenated androst-4-ene-3,6,17-triones
JO  - Steroids
A1  - Numazawa, M.
A1  - Oshibe, M.
A1  - Matsuzaki, H.
SP  - 423
EP  - 428
VL  - 58
IS  - 9
N2  - Reactions of androst-4-ene-3,6,17-trione (1) and its 19-hydroxy or 19-oxo derivative (2 or 3), suicide substrates of aromatase, with thiols were initially studied. Treatment of 4-ene-3,6-diones 1-3 with benzyl-mercaptan in MeOH at room temperature gave the corresponding 4 alpha-benzylthio-5 alpha-androstane-3,6-diones (4-6) as the major products in 24-80% yields. The C18 steroid, estr-5(10)-ene-3,6,17-trione (7), was also isolated on the treatment of 19-oxo steroid 3. Oxidation with NaIO4 and reduction with Raney Ni of the adducts gave the corresponding 4-ene-3,6-dione and desulfurized products, respectively. The results show that 19-oxygenated steroids 2 and 3 react with a thiol in a 1,4-addition manner. By means of PM3 molecular orbital calculations, the conformational features of the 19-oxygen functions of 4-ene-3,6-diones 2 and 3, 5 alpha-3,6-diones 10 and 11, and their 4 alpha-methylthio derivatives 14 and 15, model compounds of 1,4-adducts 5 and 6, were determined. In the compounds examined, the 19-hydroxy steroids favor a conformation having the hydroxyl group above the A-ring, whereas the 19-oxo substituent is oriented in the out-of-ring position (not above either A- or B-ring). These calculations suggest that compound 1 would inactivate aromatase by the same steric course of the oxygenation at C-19 as that of the natural substrate, androstenedione.<p /> <p>Language: en</p>
LA  - en
SN  - 0039-128X
UR  - http://dx.doi.org/10.1016/0039-128x(93)90082-x
ID  - ref1
ER  -