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Enzyme smooths path to planar chiral macrocycles

Good yields and enantioselectivity abide

by Leigh Krietsch Boerner
February 23, 2020 | A version of this story appeared in Volume 98, Issue 8

Two examples of the planar chiral cyclophanes that Collins’s lab synthesized.

Planar chiral molecules are relatively common in natural products, kind of funny looking, and largely ignored. Though they can be useful as pharmaceuticals or agrochemicals, they are difficult to make. Now, Shawn Collins and coworkers at the University of Montreal have developed an enzyme-catalyzed synthesis to form planar chiral molecules with high enantioselectivity (example shown) from readily available starting materials, which can be easily functionalized (Science 2020, DOI: 10.1126/science.aaz7381). The team made target compounds with up to 99% yield and 66–99% enantioselectivity. Instead of a more traditional metal catalyst, which can create toxic waste, Collins decided to look for one with a biological origin. The serine hydrolase Candida antarctica lipase B “is the organic chemist’s dream because it’s an enzyme that is superstable to high temperatures and actually more active in organic solvents than in water,” he says. The natural enzymatic pocket evolved to accommodate a secondary alcohol, so Collins was surprised that the team’s large molecules fit. But it can fit only so much, so the group couldn’t make planar chiral macrocycles with larger side groups like styrenes. But they can include halogens, he says, which are a great handle for functionalities.


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