Studies on the platinum-catalyzed exchange of hydrogen isotopes with steroids.

Investigation of the metabolism and fate of steroid hormones has been greatly facilitated by isotope stably incorporated into the substance t,o be studied. For many purposes the isotopes of hydrogen are decidedly advantageous in that the chemical synthesis of the labeled steroid can be easily and quickly achieved with a minimum of manipulation. Moreover, since the endogenous pool of the hormones cannot be very large, an excessive dilution by the glandular products will not be encountered. It should thus be possible to carry out experiments with deuterium as a tracer even though great dilutions of this element cannot be accurately measured. Likewise, the stable isotope permits use of the product in normal human subjects and, since our eventual aim was to study human steroid metabolism, the present studies were undertaken to secure hydrogen-labeled steroid hormones by a variety of chemical procedures. Earlier publications from this laboratory (14) have dealt with the preparation of steroids containing the isotopes of hydrogen and this study is an extension of a broad approach. By the use of tritium instead of deuterium, highly radioactive hormones can be prepared by the same procedures as illustrated in this report and elsewhere (5). The exchange of deuterium for hydrogen in organic compounds with metallic catalysts has been extensively studied (6-8). The introduction of deuterium into steroids with active platinum in deuterium acetic acid and heavy water was reported by Bloch and Rittenberg (9), who obtained cholesterol in 44 per cent yield with 1.9 gm. atoms of deuterium per molecule distributed nearly equally between the nucleus and the side chain. In order to use this exchange reaction as a preparative method, the scope of its application and the optimum conditions for the reaction were studied. Consideration of the studies of the catalytic exchange by other investi-