Abstract: In an effort to search for more effective irreversible agonists as new opioid receptor probes, three novel rigid opiates with flexible electrophilic chains (3,4 and 5) were designed and synthesized.Treatment of thebaine with ethyl acrylate afforded 7-α ethoxycarbonyl-6, 14-endoetheno-tetrahydrothebaine (7a) and its 7β-isomer (7b). Reduction of (7a) with LAH, tosylation of the resulting alcohol (12)with TsCl in pyridine, followed by condensation of the corresponding ester (13) with diethanolamine gave 7α-bis (2-hydroxyethyl) aminomethyl-6, 14-endo-etheno-tetrahydrothebaine (14). Compound (14) was also prepared from hydroxyethylation of corresponding amine (11), which was synthesized via four-step reaction from (7a). Treatment of (14) with boron tribromide gave the oripavine derivative (15), which was converted to the target compound 6,14-endo etheno 7α-bis (2-chloroethyl) aminomethyl-oripavine (3, α-CMO)byreaction with triphenylphosphine and carbon tetrachloride. Similarly, compound (4,α-CMT) was prepared from compound (14). Fumarylation of the alcohol (12) afforded compound (5, α-FMT), The preliminary pharmacological results showed that α-CMO and α-CMT are irreversible opioid receptor agonists in the guines pig ileum (GPI), the mouse vas deferens (MVD) and the rat brain P₂ membrane preparations. In mice α-CMO produced ultralong lasting analgesia with a duration about two days.