Kageyama M,
Tamura T,
Nantz MH,
Roberts JC,
Somfai P,
Whritenour DC,
Masamune S.
*
Massachusetts Institute of Technology, Cambridge, USA
Synthesis of Bryostatin 7.
J. Am. Chem. Soc. 1990;
112: 7407-7408
DOI:
10.1021/ja00176a058
Key words
bryostatin 7 - Julia–Lythgoe olefination - aldol reaction
Significance
The bryostatins are a family of 21 marine natural products boasting a wide range of
biological activities. They have been explored as anticancer agents, treatments for
Alzheimer’s disease, and as antivirals against HIV. Of this family, the first to succumb
to total synthesis was bryostatin 7 in a heroic synthesis by the Masamune group requiring
a total of 79 steps with a 41 step longest linear sequence.
Comment
Retrosynthetically, bryostatin 7 was broken into three fragments (A, B, and D). A and B were used for a matched aldol reaction followed by Hg-mediated cyclization. Further
manipulations yielded C. Fragment D (prepared in 22 steps) underwent a Julia–Lythgoe olefination with C to complete the unification of all fragments. A DCC-mediated macrocyclization was
used to close the lactone.
