Metabolism of three active analogues of the male antifertility agent α-chlorohydrin in the rat

Abstract

1. Two ketal derivatives of α-chlorohydrin, which possess male antifertility activity, have been synthesized labelled with ³⁶Cl. Both are metabolized by the rat to β-chlorolactic acid.

2. Neither derivative inhibited the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and triosephosphate isomerase.

3. The epoxide glycidol is metabolized to β-chlorolactic acid, presumably by first being converted to α-chlorohydrin.

4. It is proposed that the male antifertility actions of these three analogues is due to their biotransformation to α-chlorohydrin, which is then metabolized within mature sperm to a compound which is an inhibitor of glycolysis.