6-Methylenedihydrodesoxymorphine

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IUPAC_name = 4,5-α-epoxy-17-methyl-6-methylenemorphinan-3-ol

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width = 200
CAS_number = 3414-84-4
synonyms = 6-MDDM, 6-Methylenedihydrodesoxymorphine
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PubChem = 5492874
smiles = C12=CC=C(C5=C1 [C@@] 34 [C@H] (C(C2)N(C)CC3)CCC( [C@@H] 4O5)=C)O
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C = 18 | H = 21 | N = 1 | O = 2
molecular_weight = 283.36 g/mol
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6-Methylenedihydrodesoxymorphine (6-MDDM) is an opiate analogue that is a derivative of hydromorphone, where the 6-ketone group has been replaced by methylene. It has sedative and analgesic effects.

6-Methylenedihydrodesoxymorphine is a potent μ-opioid agonist, reportedly up to 80x stronger than morphine. [http://www.acsmedchem.org/module/opioid.html] Compared to morphine it has a faster onset of action and similar duration of effects. [Abdel-Rahman MA, Elliott HW, Binks R, Küng W, Rapoport H. Synthesis and Pharmacology of 6-Methylenedihydrodesoxymorphine. "Journal of Medicinal Chemistry". 1966; 9(1):1-6.] 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 which produce comparatively few side effects, [Okun R, Elliott HW. Acute Pharmacological Studies of Some New Morphine Derivatives. "Journal of Pharmacology And Experimental Therapeutics". 1958; 124(3): 255-259.] 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. [Chadha MS, Rapoport H. The Preparation of Some 6-Methylated Dihydrodesoxymorphines. "Journal of the American Chemical Society". 1957; 79(21):5730-5734.] [Wiegert PE, De La Mater G, McElheny GC, Patterson LA. Physical Constants of 6-Methylenedihydrodesoxymorphine. "Journal of Organic Chemistry". 1961; 26(12):5249-5250.]

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