This paper relates to the synthesis of the exactduplicates of opium alkaloids, and the degree of likelihood that commercial manufacture of such synthetics might make the production of opium for medical purposes unnecessary. It does not deal with the question of synthetic substitutes which have chemical structures different from those of the natural opium alkaloids.
Pages: 15 to 15
Creation Date: 1953/01/01
This paper relates to the synthesis of the exact duplicates of opium alkaloids, and the degree of likelihood that commercial manufacture of such synthetics might make the production of opium for medical purposes unnecessary. It does not deal with the question of synthetic substitutes which have chemical structures different from those of the natural opium alkaloids.
The four opium alkaloids of commercial and medical importance which are obtained from opium (or directly from the poppy plant) are morphine, codeine, thebaine and papaverine. There are a number of other "opium alkaloids" in use, but they are manufactured by conversion of morphine, codeine and thebaine. These three are closely related to each other. In fact, most of the world's supply of codeine is made from morphine, and the medically important derivatives of thebaine can also be made from codeine.
Thus it is a question of two syntheses, morphine and its relatives or derivatives on the one hand, and papaverine on the other. Scientifically, both these syntheses are now possible.
The first reported chemical synthesis of morphine was made by Marshall Gates and Gilg Tschudi, and was described in the Journal of the American Chemical Society (20 February 1952). This work also included the synthesis of codeine; in fact, the codeine was formed first and the morphine made from it. The morphine and codeine thus formed were absolutely identical with the natural alkaloids formed by the plant, Papaver somniferum.
This synthesis has no immediate possibility of practical application, as the process is much too complicated for commercial use. However, the achievement of morphine synthesis has importance in that it will be possible by variations in the process to make new substances allied to morphine, not found in nature, for experiments. It is also important in that a real understanding of the structure of morphine has finally been reached. This will make it easier not only to create new related compounds but also eventually to arrive at a simplified, commercially feasible method of making morphine itself, if that should remain a goal of research.
The first reported chemical synthesis of papaverine was made by Pictet and Gams, and was described in Comptes rendus hebdomadaires des séances de l'Académie des sciences, 149,210(1909). Papaverine can now be made commercially by several different synthetic processes and is so made whenever the supply of natural papaverine runs short.
Thus at the moment it would appear that there is no immediate prospect or problem of the general replacement of natural with artificial opium alkaloids. This can become a problem or a possibility only when a fairly simple synthesis of morphine is achieved, the papaverine problem being relatively unimportant: commercial synthetic manufacture is not likely to displace the natural papaverine in so far as the latter is a by-product of the far more important extraction of morphine from opium.