Introduction to Synthesis of Tamoxifen
As with the vast majority of drugs the biological reactions that make them effective towards disease proceed via only one isomer of the drug. In this respect Tamoxifen is no different and it is the trans isomer that is the active in the treatment of breast cancer. This cis isomer has no clinical uses and is not an oestrogen antagonist. As within the large field of drug synthesis the most successful synthesis routes will provide good yields at a reasonable cost but above all must have good stereoselecitve products. The most successful routes will be those, which are stereospecific.
There are numerous approaches to the synthesis of Tamoxifen. All of these synthetic routes show slight variations on some common reactions types. Two of the most synthesis routes.
The first is an example of a non-stereospecific synthesis and the second is the first ever-stereo specific synthesis of Tamoxifen.I have then also selected a few more routes and provided references for those, which are interested in other synthetic approaches. From this point of view both sources may be considered relatively old and may be inferior to recent approaches. However the other influence of my choice of synthetic route was the level of theory, which was applied. Both routes show the application of many synthetic reactions that are taught as first and second year undergraduate organic chemistry topics. From this point of view it is quite satisfying to witness the application of these simple reactions in the synthesis of a medicinally important and fairly complicated molecule. I have mainly considered two synthetic preparations in detail.
While searching the Internet for some interesting Tamoxifen sources I came across the above cartoon. I thought it to be quite amusing and applicable to some reaction processes (from an undergraduate's point of view anyway!)
View Synthesis Route 1 - Non-Stereospecific.
View Synthesis Route 2 - Stereospecific.
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Huw Tanner.Undergraduate Year 2 .Imperial College of Science, Technology and Medicine. CIT Project Study of Tamoxifen. |
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