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Chemists Make Cholesterol-Blocking Molecule Bisabosqual A For The First Time

Blueprint for organic synthesis is anchored by radical-mediated ring formations

by Carmen Drahl
January 14, 2013 | A version of this story appeared in Volume 91, Issue 2

Parker’s team used tandem radical cyclizations to form two of bisabosqual A’s four rings.
A reaction scheme depicting the the synthesis of Biabosqual A
Parker’s team used tandem radical cyclizations to form two of bisabosqual A’s four rings.

The mold metabolite bisabosqual A blocks an early step in cholesterol production in mammals. Its four fused rings, which come together in a cup shape, have stymied the compound’s synthesis by many chemists. But the molecule proved no match for Christopher W. am Ende, Zhou Zhou, and Kathlyn A. Parker of Stony Brook University, whose total synthesis is the first for a bisabosqual compound (J. Am. Chem. Soc., DOI: 10.1021/ja3108577). Parker’s lab previously made morphine, which has a similar shape to bisabosqual, with the established tactic of tandem radical cyclizations. Intramolecular radical chemistry circumvents the molecular crowding that can thwart formation of cup shapes by other approaches, Parker explains. Zhou and am Ende developed new conditions for radical formation involving boron and silicon reagents, and then they used the chemistry to form two of bisabosqual A’s rings and three of its five chiral centers. One of those three chiral centers doesn’t quite form selectively, however, so next on Parker’s to-do list is finding a way to better control that step. Barry B. Snider of Brandeis University, who has made the bisabosqual core, extols the work as “very elegant” and “a beautiful example of a tandem radical cyclization.”


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