Morphine molecular structure

In the first place, the structure of the target molecule is submitted to a rational analysis in order to perceive the most significant structural features, and it may be useful to use different types of molecular models at this point. It should be remembered that a molecular structure has "thousand faces" and finding the most convenient perspective may greatly simplifly the synthetic problem. The synthesis of opium alkaloids, for instance, is much simplified if one realises that they are, in fact, derivatives of benzyltetrahydroisoquinoline (18) (see Scheme 3.8). This was indeed the inspired intuition of Sir Robert Robinson which led to the structural elucidation of morphine (19) and to a first sketch of the biogenetic pathway [22], and later on to the biomimetic synthesis of thebaine 20 [23] [24]. 

Morphine, cocaine, and mescaline are all examples of drugs that occur in plants but are commonly available in refined form as white powders, sold both legally and illegally. Some of them, such as mescaline, can easily be synthesized in laboratories, but even when they are, we can still call them natural drugs because the molecules already exist in nature. Others, such as cocaine and morphine, have more complex molecular structures. Chemists can make them in laboratories, but it is not cost efficient to do so. All the cocaine and morphine on the black market and in pharmacies arc extracted from coca leaves and opium poppies. 

The molecular structure of opioids is similar to that of certain neurotransmitters that occur naturally in the brain. Because of the similarities, these drugs are able to cross the blood-brain barrier and able to occupy receptor sites used by these neurotransmitters. The brain substances are called endorphins, which is short for endogenous morphines. The endorphins are what provide our natural pain control. 

FIGURE 7.32 The molecular structures of some analgesics (a) aspirin (b) acetaminophen and (c) morphine. Note how slight the differences are among morphine, codeine, and heroin. 

An intramolecular Heck reaction was applied to the synthesis of the key intermediate for the stereoselective constmction of the rigid morphine molecular framework as depcted in the following scheme <05T513>. On the other hand, an intramolecular Heck reaction was utilized for the assembly of structurally diverse functionalized benzo[i>]furans <05SL1767>. 

J.M. Gulland and Sir R. Robinson present formulation for the molecular structure of morphine... 

Morphine-like structures and semi-rigid side chains as molecular probes for the bioactive conformation of enkephalin. 

The name of the drug morphine is derived from Morpheus, the God of dreams in Greek mythology. Morpheus is the son of Hypnos, the God of sleep, who is the namesake of the hypnotic dmgs. Morphine was isolated around 1805, but as late as 1947 the molecular structure was still not clear. The debate in those years related to the group at the C6 position. The question was settled in 1952, with the first reported synthesis of morphine. 

Figure 5.2. Molecular structure of ephedrine, an active ingredient in the traditional Chinese medicine plant Ma Huang Figure 5.3. Molecular structure of morphine...

Dezocine (30) represents a class of bridged aminotetralins possessing morphine-like analgesic properties. It appears to be roughly equivalent in potency and addiction potential to morphine. The molecule combines molecular features of precedent aminotetralins and benzomor-phans and its structure fits the classical Morphine Rule. The 1-enantiomer is the more active and the p-epimer (equatorial NHj) is the active diastereomer. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Extensive molecular dissection of the morphine molecule over the past several decades led to a host of molecules which showed narcotic analgesic activity even though they possessed but faint suggestion of the structural features present in morphine itself. Thus, both cyclic molecules such as meperidine (70) and alphaprodine (71), and acyclic Compounds such as methadone (72) were found to be effective analgesics. Common features of these compounds were formalized by the Beckett-Casy rule, which states as minimal required structural features (a) an aromatic ring attached to... 

The PE spectra of some other alkaloids like methadone and the opiate narcotics morphine, codeine and heroin have been investigated by Klasinc and coworkers95. Also in this study structure-activity relationships based on IPs were sought but not found. Since the interaction of the drug molecule with the receptor is highly specific, it is not unreasonable that the molecular rather than the electronic structure is more important for the physiological activity. 

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