Synthesis of [3H]-cycloalkanoprogesterones (pregna-d'-pentaranes) and study of their interaction with a progesterone receptor

Abstract

tn order to search target organs and to study the mechanism of the action of steroids with separated biological functions, tritium-labeled pregna-D'-pentaranes were synthesized by an original procedure, and their interaction with a progesterone receptor was investigated. The uterine progesterone receptor was shown to be the only specific binding protein for these compounds.

The Synthesis of Tritium-Labeled 16α,17α-Cyclohex-3′-eno-progesterone as Probe for the Study of Steroid–Receptor Binding

“…More detailed study of PR binding using tritium-labeled pentaranes 1 and 2 showed that this contradiction appears to arise from overestimation of the active concentration of the hydrophobic pentaranes due to high adsorption on tube walls (4). To obtain reliable data on binding of pentaranes to PR and account for their adsorption on tube walls it was necessary to use tritiated pentaranes with a relatively high specific radioactivity (5).…”

“…Lindlar catalyst and tris-triphenylphosphine (I) rhodium chloride were purchased from Fluka. Standard steroids were synthesized as described earlier (5). Analysis and purification of preparations was performed by HPLC and TLC (Table 1).…”

“…16␣,17␣-Cyclohexanoprogesterone (1) possess a high activity both in the proliferation of endometrium (Clauberg-McPhail test) and in the maintenance of pregnancy (Corner-Allen's test) while 16␣,17␣-cyclopropano-, 16␣,17␣-cyclobutano-, and 16␣,17␣-cyclopentano-progesterones (2, 3 and 4, respectively), keeping the same proliferation effect, proved to be less effective in the pregnancy maintenance test (Scheme 1). On the other hand, 16␣,17␣-cyclohex-3Ј-eno-progesterone (5), with a weak effect on proliferation, proved to be very active in the pregnancy maintenance test.…”

Steroids: reactions and partial synthesis

“…133 The preparation of various 16a,17a-isooxazoline derivatives of prednisolone such as 65 has been reported 134,135 in the course of work on novel antiinflammatory steroids whilst work on the synthesis of 16a,17acyclohexanopregnanes such as 66 and their interaction with the progesterone receptor, has continued. 136,137 The introduction of functionality at C-21 is important in the context of a number of steroidal biological activities. The effect of C-16 substituents on the formation of C-20 silyl 20(21)-enol ethers has been examined.…”