Asymmetric Total Synthesis of Aglacins A, B, and E

Abstract

An asymmetric photoenolization/Diels-Alder (PEDA) reaction between electron-rich 2-methylbenzaldehydes and unsaturated g-lactones was developed to directly construct the basic tricyclic core of aryltetralin lactone lignans. This methodology enabled the first asymmetric total synthesis of aglacins A, B, and Ea nd revision of the absolute configuration of these natural lignans.T he strategy was also used to prepare the naturally occurring aryldihydronaphthalene-type lignans (À)-7,8-dihydroisojusticidin Ba nd (+ +)-linoxepin in four and six steps,aswell as 27 natural-product-like molecules containing aC 8 ' quaternary center.W eb elieve that the synthetic aglacins and small-molecule library providen ew opportunities to carry out the SAR studies of the podophyllotoxinf amily of natural products.

Taming the radical cation intermediate enabled one-step access to structurally diverse lignans

“…Overall, this represents a two-step total synthesis of aglacins E (4), F (5), and a three-step synthesis of aglacin A (6) from 3,4,5-trimethoxyphenyl cinnamic alcohol. We note that Gao's group has recently communicated an elegant asymmetric total synthesis of aglacins E (4), A (6), and B (3) in 13-and 14steps, respectively 21 .…”

“…Notwithstanding the great progress recorded in the synthesis of lignans 14 , a concise and divergent synthetic approach allowing access to diverse subsets of lignan scaffolds from simple and cheap starting materials is still highly demanded in order to fully exploit the biological potential of these natural products [15][16][17][18][19][20][21] . While the structures of lignans are relatively simple, the control of stereochemistry in the cyclization step remains challenging [22][23][24][25][26] .…”