Many such derivatives have an epoxy group between carbons 4 and 5 (i.e., 4α,5α-epoxy), thereby forming an E ring.
The substitution of certain bulky groups on nitrogen 17 converts an opioid agonist into an opioid antagonist, the most important of which is naloxone, a non-selective opioid antagonist with no opioid agonist properties whatsoever.