Proxorphan Synthesis
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Proxorphan ( INN), also known as proxorphan tartate ( USAN) (developmental code name BL-5572M), is an opioid
analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
and antitussive
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
of the morphinan family that was never marketed. It acts preferentially as a κ-opioid receptor partial agonist and to a lesser extent as a μ-opioid receptor partial agonist.


Synthesis

Starting material for this preparation is ketoester 1, available by one of the classical benzomorphan syntheses. Condensation with the ylide from Triethyl phosphonoacetate (
HWE reaction Hwe or HWE may refer to: * Hwe (Cyrillic), a letter of the Cyrillic script * Hwe language, spoken in Ghana, Togo, and Benin * Hardy–Weinberg equilibrium * Home War Establishment of the Royal Canadian Air Force * Horner–Wadsworth–Emmons rea ...
) affords diester 2. Catalytic hydrogenation proceeds from the less hindered face to afford the corresponding saturated diester (3). The esters are then reduced by means of LiAlH4 to give the glycol (4); this undergoes internal ether formation on treatment with acid to form the pyran ring of 5. Von Braun reaction with BrCN (or ethyl chloroformate) followed by saponification of the intermediate leads to the 2° amine (6). This is converted to the cyclopropylmethyl derivative 8 by acylation with cyclopropylcarbonyl chloride followed by reduction of the thus formed amide (7) with LiAlH4. Cleaving off the O-methyl ether with sodium ethanethiol affords proxorphan (9).


See also

* Butorphanol *
Cyclorphan Cyclorphan is an opioid analgesic of the morphinan family that was never marketed. It acts as a μ-opioid receptor (MOR) weak partial agonist or antagonist, κ-opioid receptor (KOR) full agonist, and, to a much lesser extent, δ-opioid receptor ...
*
Ketorfanol Ketorfanol (International Nonproprietary Name, INN, United States Adopted Name, USAN) (developmental code name SBW-22), or ketorphanol, is an opioid analgesic of the morphinan family that was found to possess "potent antinociception, antiwrithing ...
*
Levallorphan Levallorphan ( INN, BAN) (brand names Lorfan, Naloxifan, Naloxiphan), also known as levallorphan tartrate (USAN), is an opioid modulator of the morphinan family used as an opioid analgesic and opioid antagonist/antidote. It acts as an antagonist ...
* Levomethorphan * Levorphanol * Moxazocine * Nalbuphine *
Oxilorphan Oxilorphan (INN, USAN) (developmental code name L-BC-2605) is an opioid antagonist of the morphinan family that was never marketed. It acts as a μ-opioid receptor (MOR) antagonist but a κ-opioid receptor (KOR) partial agonist, and has similar e ...
*
Xorphanol Xorphanol (INN) (developmental code name TR-5379 or TR-5379M), also known as xorphanol mesylate (USAN), is an opioid analgesic of the morphinan family that was never marketed. Xorphanol is a mixed agonist–antagonist of opioid receptors, acti ...


References

Analgesics Antitussives Benzomorphans Kappa-opioid receptor agonists Opioids Phenols {{analgesic-stub