The Conversion of Pregnanes to Androstanes

A chronological examination of the steroid literature regarding the conversion of pregnanes to androstanes, androstanes to pregnanes, and the side-chain polyoxygenation of pregnanes reveals, in microcosm, the history of the development of steroid chemistry over the past three decades. 

Conversion of pregnanes to androstanes via the Schmidt Rearrangement 17/3-aminoandrost-5-en-3/3-ol, 145 Cyclobutanol formation by ketone irradiations... 

Recent improvements in the total synthesis of steroids which give as the first tetracyclic products 19-norsteroids bearing a hydroxyl or keto group at C-17 have revived interest in the conversion of androstanes to pregnanes. 

The reaction of 17-keto steroids with hydrogen cyanide (or acetone cyanohydrin) to form a mixture of the 17-cyano-17-hydroxy compounds, followed by dehydration and reaction with methyl Grignard reagent, is one of the earliest methods for the conversion of androstanes to pregnanes. 

Conversion of androstans to pregnanes via the Reformatsky Reaction 17a-pregn-5-ene-3/3,17/3,21-triol and ethyl 3/3-acetoxy-17/3-hy droxy-17a-pregn-5-en-21-oate, 139... 

Induction of CYP-mediated metabolism requires prior exposure of the hepatocyte s CYP-synthesis mechanism to a chemical inducer. The inducer signals the synthetic mechanisms to upregulate the production of one or more CYP isoforms, a process that takes time. Consequently, evidence of increased CYP activity is of slow onset following initiation of exposure to the inducer, and conversely slowly reverts to baseline after the inducer is removed (46,47). Enhancement of CYP expression/activity due to chemical induction therefore reflects prior, but not necessarily current, exposure to the inducer. Nuclear receptors, such as the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), have been identified as key elements in the process of transcriptional activation (48-56). 

---