Total Synthesis Highlights
Total Synthesis Highlights
Total Synthesis Highlights
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Controlled desilylation of 11 followed by selective oxidation delivered the seco acid 12. It had<br />
previously been shown by others that some cyclic protecting groups facilitate macrolactone<br />
formation, while others do not. Fortunately, the two cyclic protecting groups of 12 served well,<br />
and the macrolactonization proceeded efficiently. Protecting group removal and reductive<br />
unmasking of the hydroxy ketone then delivered erythronolide A (4).<br />
Overall, this elegant synthesis is a showcase for the iterative use of the 1,3-dipolar cycloaddition<br />
of enantiomercially-pure allylic alcohols for the preparation of extended arrays of acyclic<br />
stereogenic centers.<br />
57. The Boger Route to (-)-Vindoline<br />
The Vinca-derived vinblastine (2a) and vincristine (2b) are still mainstays of cancer chemotherapy.<br />
The more complex half of these dimeric alkaloids, vindoline (1), has in the past presented a<br />
formidable challenge for total synthesis. Dale L. Boger of Scripps, La Jolla has developed (Org.<br />
Lett. 2005, 7, 4539.) a strikingly simple solution to this problem, based on sequential<br />
cycloaddition.<br />
The starting point for the synthesis was N-methyl 6-methoxytryptamine (3), an improved<br />
preparation of which is described by the authors. This was extended to 4, which was then cyclized<br />
to 5, and acylated with 6 to give 7. On heating, 7 cyclized to 8, which lost N 2 to give the<br />
zwitterion 9. Addition of the intermediate 9 to the indole then gave 10. In one reaction, the entire