The structure of morphine was worked out in 1925 by English chemist Sir Robert Robinson. He was also responsible for working out the structure of strychnine in 1946.
C == C C - N - CH3
/ \ : /
HO - C C -:-C
\ / : \
C -- C ...C C
| \ /
| C == C
| / \
O -- C C
\\ //
C -- C
/
HO
Morphine
The C5-N-CH3 ring structure in morphine is called a piperidine. The ring formed by oxygen and the four carbons is called a furan.
OH
|
C = O C == C C - N - CH3
| / \ : /
CH2-O - C C -:-C
\ / : \
C -- C ...C C
| \ /
| C == C
| / \
O -- C C
\\ //
C -- C
/
O
\
CH2 - C = O
|
OH
Heroin (3,6-diacetylmorphine)
Heroin is a highly addictive drug, being twice as active as morphine. The reason may be because its increased
lipophillic character results in better trasport characteristics.
C == C C - N - CH3
/ \ : /
HO - C C -:-C
\ / : \
C -- C ...C C
| \ /
| C == C
| / \
O -- C C
\\ //
C -- C
/
O
\
CH3
Codeine (Methylmorphine)
Codeine has about one-tenth the effect of morphine if given
parenterally, because it must be partially demethylated in the
liver and thus transformed into morphine. Given intracerebrally it is totally inactive as an
analgesic.
Morphine -OH
Heroin -2(OCH2COOH)
Codeine -OCH3
We can see from the structures of heroin and codeine above how altering one or two functional groups on the morphine molecule vastly affect its activity.
Work has been done on the structure of morphine for years, with the aim of increasing its activity and at the same time reducing its addictive properties. The molecules produced in this fashion are called synthetic morphine analogues.
One incredibly successful synthetic morphine analogue is (-)levorphanol.
C == C C - N - CH3
/ \ : /
C C -:-C
\\ // : \
C -- C ...C C
\ /
C == C
/ \
C C
\\ //
C -- C
/
HO
Levorphanol
Eliminating the furan (the oxygen "bridge") from morphine, creates compounds called Morphinans, such as Levorphanol, which is five to six times more active than morphine.
Perhaps the most successful group of synthetic morphine analogues has been the piperidine derivatives. They represent the ultimate simplification of the morphine skeleton. They were first developed in the 1940's and one, meperidine (Demerol) is perhaps the most widely used synthetic opiate in clinical practice despite its addictive properties.
C - N - CH3
| |
C == C C C
/ \ | |
C C - C - C
\\ // |
C -- C C = O
|
O
C2H5
Meperidine (Demerol)
References:
Medicinal Chemistry. Nogrady, T. 1988 (second edition) Oxford University Press.
Physiocochemical Principles of Pharmacy. Florence, AT & Attwood, D. 1994 (second edition) MacMillan Press.
Clinical Chemisty in diagnosis and treatment. Mayne, PD. 1994 (sixth edition) Edward Arnold, London.