Assignment on

Source, stereochemistry, medicinal values and structural elucidation of Morphine

Submitted to: Mr. Ashwinee Shrestha, Department of Pharmacy School of Science Kathmandu University

Submitted by: Amik Tuladhar, Roll-18 M. Pharm. 1st Year 2nd Semester (Batch 2010)

Submission date: 18.09.2011

Morphine is the most important of the opium alkaloids. Morphine has hydrophenanthrene skeleton with fused N-methyl-piperidine ring and contains a phenolic and an alcoholic hydroxyl groups. Past the optimum point for extraction. Papaver somniferum. Morphine is generally 8 to 17 percent of the dry weight of opium. Finally. and in some cases negligible amounts of hydromorphone. poppy. which are used in the manufacture of semi-synthetic and synthetic opioids like oxycodone and etorphine and some other types of drugs.04 percent. they being strongly hypnotic. bracteatum does not contain morphine or codeine. Codeine is considerably less toxic and involves much less danger from habit formation. thebaine and oripavine. perhaps down to 0. Occurrence of morphine in otherpapaverales and papaveraceae. or common and/or edible. and other poppy derivatives. dihydromorphine. Codeine and its salts are narcotic. including the 'Przemko' and 'Norman' cultivars of the opium poppy. tetrahydrothebaine and hydrocodone (these compounds are rather synthesized from thebaine and oripavine). various processes in the plant produce codeine. The latter varieties. It was first isolated from opium by Serturner in 1816 and elucidation of its structure became the goal of many researchers.bridge extending from C-9.Heroin is prepared by acetylation of morphine. the dried sap (latex) derived from shallowly slicing the unripe seedpods of the opium. stereochemistry. as well as in some species of hops and mulberry trees has not been confirmed.Source. A formula proposed by Gulland and Robinson in 1925 was secure in all respects except the position of anchoring ethanamine. Morphine was the first active principle purified from a plant source and is one of at least 50 alkaloids of several different types present in opium. Poppy Straw Concentrate. although specially-bred cultivars reach 26 percent or produce little morphine at all. Their use tends to habit formation. or other narcotic phenanthrene-type. are used to produce two other alkaloids. dihydrocodeine. alkaloids. Morphine is produced most predominantly early in the life cycle of the plant. Morphine and its derivatives are classified as narcotic analgesics. a total synthesis of morphine was done by Gates in 1952. and established that the chain is indeed linked at C-13. P. analgesics and antitussive. . thebaine. under 1 percent. This species is rather a source of thebaine. medicinal values and structural elucidation of Morphine Source of morphine Morphine is the most abundant alkaloid found in opium.

34 is the structure of morphine. The starting material was dihydrocodeine. which was subjected to ozonolysis. Morpheus. 6. Since the gross structure of dihydrocodeine was already known. This ozonide was worked up and subsequently reduced with lithium aluminium hydride (LAH) to obtain a tetrahydroxy compound (2. (codeine. Its acetylation leads to the formation of Heroin.2-diol.13 and 14. which is the monomethyl ether of morphine is also a constituent of opium). It can be seen that there are five chiral centers in this structure.4) which behaved as a 1. 4.9. Its structure was the subject of several investigations which ultimately led to its formulation as shown in the figure above. at positions 5. the structure of this tetraol could be figured out as shown below: . It is a constituent of opium. Stereochemistry of morphine Fig: Structure of Morphine The morphine is named after the Greek god of sleep.Here.1. The most convincing experimental evidence with regard to the relative configurations at C5 and C6 was generated by Rapoport and co-workers by selectively ‘burning out’ the benzene ring.

Relating the configurational centers at C6 and C13.1. the corresponding nitrogen-free.1. in codeine.5). the C6 hydroxyl and the C13-C15 bond should be trans to each other as they are on the same side in isocodeine. On the other hand. unsaturated compound (2. in dihydrocodeine. The C13-C15 bond and the C9-N bond should be on the same side of the middle ring as they are an integral part of the bridged . reactions of 1. it failed to give any cyclic ether.9) similarly obtained from dihydrocodeine was not affected by acids.6) obtained from dihydroisocodeine (2. The chiral centers C9 and C13 could be readily related to each other. in agreement with this logic. nitrogen-free compound (2.1. it would perhaps be useful to recall the differences in rates of reaction between cis and trans cyclohexane 1.1. For the formation of such ether. followed by catalytic hydrogenation and a second Hoffmann reaction. an unsaturated. Therefore. as expected.1.2-diols with lead tetraacetate and periodic acid are more amenable to quantitative analysis. it could be considered as a cyclohexane 1. was not as straight forward as relating C5 and C6.8).7) which underwent a facile acid-catalyzed rearrangement to give a cyclic ether (2.2-diols. On the other hand. Dihydroisocodeine (2.2-diol derivative. the hydroxyl at position C6 and the newly formed vinyl group at C13 in the end-product should be on the same side of the ring.5) by an identical series of reactions was found to be three times less reactive towards lead tetraacetate. At this point. which are not adjacent but close enough. the corresponding tetrahydroxy compound (2.1. yielded. The cis compound is also known to react faster with acetone and to increase the conductivity of boric acid to a larger extent. However. on Hoffmann exhaustive methylation. Therefore.Thus. That the two hydroxyls in this part of the molecule were cis to each other was indicated by the facile reaction of the compound with lead tetraacetate. the C5-oxygen bridge and the C6 hydroxyl should be cis to each other.

Structural elucidation of Morphine The presence of a hydrophenanthrene ring system was suggested in 1881 by the isolation of phenanthrene as a product of zinc dust distillation of morphine. This reaction is shown below: .bicyclic system which could only be cis fused. Perhaps the most difficult part of the chemical approach towards delineating the stereochemistry of morphine and its derivatives was to devise a suitable strategy to relate C13 and C14. The location of the three oxygen functions was established by degradation leading to phenanthrene derivative oxygenated at 3.5 positions as shown in figure below. Medicinal values of Morphine Morphine was used to relieve pain and diarrhea experienced by the soldiers living in deplorable conditions while at war. Morphine on heating with hydrochloric acid gave apomorphine. Morphine is commonly used in hospitals for the management of postoperative and chronic pain. The medicinal use of morphine remains an integral.4. but strictly regulated. part of clinical medicine.

. This is one of a variety of color tests that are used. If morphine and the reagent react. changing to blue. Forensic scientists exploit a group characteristic property of morphine and its related compounds: a peculiar reaction with Mecke's (or Lafon's) reagent. meaning that they suggest the presence of opiates but don't absolutely prove it. Final confirmation is obtained through instrumentation. however. next slowly to bluish green with a yellow-brown edge. the following colors appear: green. are presumptive tests. either gas chromatography-mass-spectrometry or by Fourier Transform Infrared Spectroscopy.The 1914 Harrison Narcotics Tax Act in the United States made possession of morphine a criminal act. Most. NMR has also been used to identify heroin. then quickly a greenish blue. The reagent consists of selenious acid (H2SeO3) in concentrated sulfuric acid (H2SO4). then finally olivaceous green.

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Triggle. Morphine By Gregory D. R.qc. J. Pg.emsb. Nagasampagi. 19 (structural 3. 49 5. 258 4. Pg.org/wiki/Morphine 2.pdf elucidation) Sivakumar. http://media.html .wiley. Krishnaswamy. Bhimsen A.References 1.ca/laurenhill/science/morphine. http://en. http://www. Pg.wikipedia. Meenakshi 6. Busse.com/product_data/excerpt/4X/35273144/352731444X. Bhat. Chemistry of natural products By Sujata V. D. Chemistry of natural products: a unified approach By N.

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