Taxol molecular targets

Figure 5.29. PAMAM dendrimer multifunctional conjugates for cancer treatment. The FA group is a folic acid cancer cell target, and FITC is fluorescein isothiocyanate, used as an imaging agent. Also shown (bottom) is the molecular structure for the anticancer drug, taxol, denoting the -OH group that covalently attaches to the dendrimer. Reproduced with permission from Majoros, I. J. Myc, A. Thomas, T Mehta, C. Baker, J. R. Biomacromolecules, 2006, 7, 572. Copyright 2006 American Chemical Society.

Clearly, molecular chemists in general are able to elaborate more and more complex species, as beautifully demonstrated by the synthesis of amazingly complicated natural products. For instance, the total synthesis of compounds such as taxol and brevetoxin B represents a formidable tour de force, as does that of many other recent examples. However, most of the time, once the compound has been made, the target has been reached. 

Photosubstrate 69 was an intriguing and optimistic approach with all but two carbons of the tetracyclic taxol target. Unfortunately, this bis-2-pyridone did not photocyclize to 70 but only slowly decomposed photochemically. We speculated that the obstacle to this cycloaddition was the requirement that four fiilly substituted sp carbons be created in a single step. Molecular modeling reinforced this view. ... 

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