Total Synthesis of Brevenal

Abstract

This manuscript describes the total synthesis of the marine ladder toxin brevenal utilizing a convergent synthetic strategy. Critical to the success of this work was the use of olefinic-ester cyclization reactions and the utilization of glycal epoxides as precursors to C–C and C–H bonds.

Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome

“…11 This lack of stereoselectivity was somewhat unexpected, especially given the presence of chelating atoms at both α and β positions of ( R )-isopropylidene glyceraldehyde. In an attempt to improve anti -diastereoselectivity, we investigated this addition reaction in the presence of a number of Lewis acids such as CeCl 3 12 , ZnCl 2 13 and MgBr 2 14 , in THF and ether. However, there was no further improvement in the diastereomeric ratio.…”

Recent progress in neuroactive marine natural products

“…106, 107 Recently, four more syntheses for brevenal were published that likely will afford more convergent routes to prepare this potentially useful compound. 108–111 …”

A Short Sequence for the Iterative Synthesis of Fused Polyethers

“…They are also of interest because of their potent biological activities. Total syntheses of the brevetoxins, [22][23][24][25][26] ciguatoxins, [27][28][29][30][31][32][33] gambieric acids, [34,35] gymnocins, [36,37] gambierol [38][39][40][41][42] and brevenal [43][44][45] have been accomplished, but syntheses of the larger natural products (i. e., those that possess more than eight rings) are generally extremely lengthy and cannot provide sufficient quantities of the natural products for full biological evaluation or extensive analogue synthesis. Consequently, new strategies for the rapid construction of fused polyethers are required to reduce the step count significantly and improve both synthetic convergence and efficiency.…”