Amino- and dienamino-derivatives formed from adrenocortical steroids and heterocyclic bases

Abstract

Pyrrolidine, morpholine, and piperidine react directly with the 20-oxo-17α, 21-dihydroxy-side-chain of corticosteroids to give 21-amino-derivatives. l.r. and n.m.r. data indicate the presence of an internal hydrogen bond between the 17α-hydroxy-group and the C-21 nitrogen atom. The reaction at the 4-en-3-one system leads, as expected, to 3-amino-3,5-dienes. Reactivity at C-3 follows the order pyrrolidine > morpholine > piperidine and can be explained on the basis of resonance theory and steric effects. It is possible to prepare either 21-amino-or 3,21-diamino-derivatives. An s-trans-structure is postulated for the 3,5-diene system; a cross-conjugated system is excluded on the basis of n.m.r. data. Corticosteroids without a 17α-hydroxy-group react at C-21 only, under more drastic conditions. A possible explanation of the function of the 17-hydroxy-group is advanced.