6-Methylenedihydrodesoxymorphine

6-Methylenedihydrodesoxymorphine
Clinical data
Other names	6-MDDM, 6-Methylene- dihydrodesoxymorphine
Identifiers
	IUPAC name 4,5-α-Epoxy-17-methyl-6-methylenemorphinan-3-ol;
CAS Number	3414-84-4 ;
PubChem CID	5492874;
ChemSpider	4591200 ;
CompTox Dashboard (EPA)	DTXSID20187741 ;
Chemical and physical data
Formula	C18H21NO2
Molar mass	283.371 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Oc2c1O[C@H]5\C(=C)CC[C@H]4[C@@H]3N(CC[C@@]45c1c(cc2)C3)C;
	InChI InChI=1S/C18H21NO2/c1-10-3-5-12-13-9-11-4-6-14(20)16-15(11)18(12,17(10)21-16)7-8-19(13)2/h4,6,12-13,17,20H,1,3,5,7-9H2,2H3/t12-,13+,17-,18-/m0/s1 ; Key:LBCZKDPFDXFDTN-GGNLRSJOSA-N ;
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6-Methylenedihydrodesoxymorphine (6-MDDM) is an opiate analogue structurally related to desomorphine that is a derivative of hydromorphone, where the 6-ketone group has been replaced by a methylidene group. It has sedative and analgesic effects.

6-Methylenedihydrodesoxymorphine is a potent μ-opioid agonist, 80x stronger than morphine.^[1] Compared to morphine it has a faster onset of action and similar duration of effects.^[2] It produces around the same degree of respiratory depression as morphine, but less inhibition of gastrointestinal motility. Animal studies show it to be a potent analgesic which produces significant analgesic effects even at low doses while inducing comparatively few side effects,^[3] however it has never been developed for medical use in humans.

6-Methylenedihydrodesoxymorphine is synthesised in two steps; first a Wittig reaction is used, reacting hydrocodone with methylenetriphenylphosphorane and an alkyl lithium reagent in diethyl ether to form 6-Methylenedihydrodesoxycodeine. The 3-methoxy group is then cleaved to hydroxy, by reaction with pyridine. The second step tends to be incomplete and often gives fairly low yields, but these can be improved by changing the reaction conditions.^[4]^[5]

References

^ Woster PM. "Chemistry of Opioid Analgesics". PHA 4220 - Neurology Pharmacotherapeutics, Medicinal Chemistry Tutorials. Archived from the original on July 16, 2007.
^ Abdel-Rahman MA, Elliott HW, Binks R, Küng W, Rapoport H (January 1966). "Synthesis and pharmacology of 6-methylenedihydrodesoxymorphine". Journal of Medicinal Chemistry. 9 (1): 1–6. doi:10.1021/jm00319a001. PMID 4163617.
^ Okun R, Elliott HW (November 1958). "Acute pharmacological studies of some new morphine derivatives". The Journal of Pharmacology and Experimental Therapeutics. 124 (3): 255–9. PMID 13588539.
^ Chadha MS, Rapoport H (1957). "The Preparation of Some 6-Methylated Dihydrodesoxymorphines". Journal of the American Chemical Society. 79 (21): 5730–5734. doi:10.1021/ja01578a040.
^ Wiegert PE, De La Mater G, McElheny GC, Patterson LA (1961). "Physical Constants of 6-Methylenedihydrodesoxymorphine". Journal of Organic Chemistry. 26 (12): 5249–5250. doi:10.1021/jo01070a541.

[1] Woster PM. "Chemistry of Opioid Analgesics". PHA 4220 - Neurology Pharmacotherapeutics, Medicinal Chemistry Tutorials. Archived from the original on July 16, 2007.

[pmid4163617-2] Abdel-Rahman MA, Elliott HW, Binks R, Küng W, Rapoport H (January 1966). "Synthesis and pharmacology of 6-methylenedihydrodesoxymorphine". Journal of Medicinal Chemistry. 9 (1): 1–6. doi:10.1021/jm00319a001. PMID 4163617.

[pmid13588539-3] Okun R, Elliott HW (November 1958). "Acute pharmacological studies of some new morphine derivatives". The Journal of Pharmacology and Experimental Therapeutics. 124 (3): 255–9. PMID 13588539.

[4] Chadha MS, Rapoport H (1957). "The Preparation of Some 6-Methylated Dihydrodesoxymorphines". Journal of the American Chemical Society. 79 (21): 5730–5734. doi:10.1021/ja01578a040.

[5] Wiegert PE, De La Mater G, McElheny GC, Patterson LA (1961). "Physical Constants of 6-Methylenedihydrodesoxymorphine". Journal of Organic Chemistry. 26 (12): 5249–5250. doi:10.1021/jo01070a541.

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See also

References