Morphine analogs

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

Some of the morphine analogs can occasionally he hallucinogenic. Nulline (Nalorphine) used to monitor heroin use, M285 (Cypren-orphine) and cyclazocine are some of the better known examples. See the Merck Index for references to the synthesis of these compounds. 

Morphine Analogs — Psychopharmacologia 30,108(1978) describes a thebaine derivative, active at less than 1 00 micrograms, which produced a trip described as a combination of downers, LSD and itching powder. 

Oxymorphone Hypersensitivity to morphine analogs acute asthma attack severe respiratory depression or upper airway obstruction paralytic ileus pulmonary edema secondary to a chemical respiratory irritant. 

Morphine s licit use is as an analgesic and for the production of semisynthetic morphine analogs. Approximately 90% of the licit morphine produced is used to make codeine codeine... 

Figure 2.3 Dextromethorphan 6, the unnatural enantiomer of a narcotic morphine analog, is an antitussive drug. The antidiarrhea drug loperamide 7 and the neuroleptic drug haloperidol 8 also resulted from structural modification of morphine. The morphine antagonist nalorphine 9 differs from the opioid agonist morphine 3 (Figure 2.2) only by having an N-allyl group instead of the N-methyl group.

The 6-oxo group of 14-hydroxycodeinone may be converted directly to an oxime, which may be hydrogenated over Pd-C to 88 and then to corresponding morphine analogs. Compound 88 was claimed to have a selective antitussive activity and analgesia of long duration.085 ... 

A semisynthetic route to morphine analogs was found (10) from thebaine (8) using Diels-Alder reactions in the C-ring. Adducts such as (9)have the distinction of enormous potency (U), sufficient to immobilize rhinoceroses at moderate dose levels Unfortunately, the addictive liability runs parallel to the increase in analgesic potency, a tendency that was partly overcome (12) in the analog buprenorphine (10). 

The following synthetic sequence recently appeared as the key part of a synthesis of some morphine analogs. Draw reasonable mechanisms for each step. Dbs = 2,6-dibenzosuberyl, a protecting group for N. 

Modification of the N-substituent of the potent morphine analog oxymorphone has led to several compounds with antagonist activity. 

Nonaqueous capillary electrophoresis has been applied to the separation of basic drugs (316). Efficient, rapid, and versatile conditions were obtained with 20 mM ammonium acetate in acetonitrile-methanol-acetic acid (49 50 1). Baseline separations of 9 morphine analogs, 11 antihistamines, 11 antipsychotics, and 10 stimulants could each be obtained within 6 min. Migration times for individual components had Relative Standard Deviation between 0.8% and 3.5%. Using an internal reference, normalized peak areas were between 2.2% and 9.1%. The precision data was reported to be instrument dependent, since excellent results were obtained only when the instrument had precise evaporation- and temperature-control systems. 

Synthetic approaches to novel morphine analogs Turner, Stephen Michael... 

New method for synthesis of tricyclic morphine analog Zhang, Yongmin Zhang, Lihe Liu, Weiqin Thai, C. Labidalle, S. 

Morphine analogs derived from tetra- and hexahydrobenzofurans. II. Synthesis and stereoselective functionalization of dibenzofurans... 

Morphine analogs derived from tetra-and hexahydrobenzofurans. 1. Synthesis and stereospecific epoxidation of arylalkylcyclohexane intermediates Labidalle, Serge Min, Zhang Yong Reynet, Annick Moskowitz, Henri ... 

Improved synthesis of 3-substituted 7-methoxybenzofurans. Useful intermediates for the preparation of morphine analogs of organic chemistry... 

Synthesis of morphine analogs with a tetrahydrodibenzofuran skeleton... 

Synthesis and kinetic study of the hydrolysis of 4-cyano-4-phenylpiperidines access to morphine analogs Gervais, Christian Anker, Daniel Chareire, Martine Pacheco, Henri Bull. Soc. Chim. Fr. (1979), (5-6, Pt. 2), 241-8... 

Synthesis of morphine analogs. Part 2 Substituted pyrrolo[3,4-h]isoquinolines Lindsay Smith, John R. Norman, Richard O. C. Rose, Malcolm E. Curran, Adrian C. w. Lewis, John W. 

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