Metabolism of Anabolic Androgenic Steroids Created by James Campbell and David Takapu Edited by Margaret Hilton Honors Organic Chemistry Chem 2321 (Sigman), 2013

Introduction Metabolism prepares for excretion Anabolic androgenic steroid Used by athletes, screened for by analytical chemists Reference: http://www.clinchem.org/content/42/7/1001.full.pdf

Phase I Metabolism Overview: Liver cells hydroxylate, reduce, and oxidize anabolic androgenic steroids in order to make them more hydrophilic. Once the steroids are hydrophilic, they can be excreted from the body. Examples Although not shown here, hydroxylation can occur at many other carbons. Reference: http://www.clinchem.org/content/42/7/1001.full.pdf

Phase II Metabolism Overview: This phase is also called conjugation. Conjugation involves the addition of a glucose or sulfate group to certain alcohols in order to increase the hydrophilicity of the molecule. Examples Glucuronidation cannot always occur on tertiary alcohols due to steric hindrance within the enzyme. These tertiary alcohols are always sulfated in Phase II Metabolism. Reference: http://www.clinchem.org/content/42/7/1001.full.pdf

Phase II Metabolism Side mechanisms of Phase II Metabolism Mechanism Reference: http://www.clinchem.org/content/42/7/1001.full.pdf

Questions 1 and 2 Alcohols can be protected with silyl groups, such as with MSTFA, as shown above. When steroids are screened using GC/MS, the alcohols and ketones are first protected using MSTFA to prevent side reactions in the column. You found Molecule 2 after derivatizing with MSTFA the urine of an athlete found positive for Drostanolone. Propose a mechanism for the reaction of Drostanolone in MSTFA to form Molecule 2. It has been published that the 17 hydroxyl on the steroid 4-chloro1,2-dehydro-17a-methyltestosterone is sulfated during metabolism. You found metabolites 1 and 2 in the analysis of an athlete's urine who tested positive for this steroid. Propose mechanisms for the two reactions.

Questions 3 and 4

Contributed by: Created by James Campbell and David Takapu (Undergraduates) Edited by Margaret Hilton Honors Organic Chemistry Chem 2321 (Sigman), 2013 University of Utah