Enantioselective synthesis of spirocyclic nitrogen-containing heterocycles catalyzed by an iridium-containing cytochrome
Data files
Aug 06, 2025 version files 14.56 MB
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CD.xlsx
53.17 KB
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final_kinetic.xlsx
5.64 MB
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kinetic_2.xlsx
8.48 MB
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README.md
2.50 KB
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UV-vis.xlsx
19.87 KB
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VCD_DFT_calc.txt
356.66 KB
Abstract
In the last decade, thousands of synthetic building blocks, intermediates, and drug candidates containing a spirocyclopropane core with at least one nitrogen atom have been investigated for a range of biological activities. These compounds create three-dimensional architectures that maintain the rigidity of their more sp2-rich analogs, but most examples contain simple core structures with unsubstituted cyclopropyl moieties, and they require lengthy syntheses. Therefore, a straightforward method to produce more complex spirocyclic amines with high stereoselectivity would be of great synthetic utility. Here we report the stereoselective cyclopropanation of methylene-substituted, saturated heterocycles catalyzed by an iridium-containing cytochrome. After just four rounds of mutagenesis, we produced spiroazetidines, spiropyrrolidines, and spiropiperidines with up to 99% ee. These results demonstrate an expeditious route to valuable, rigid, sp3-rich amino acid linchpins.
https://doi.org/10.5061/dryad.w6m905r1c
Description of the data and file structure
CD.xlsx
This file contains the raw CD data taken for the starting variant and the most evolved variant. XYDATA_nm is the wavelength. Measurement is taken in millidegree and then converted to molar ellipticity by molecular weight, path length, and concentration, which are all incorporated in the (molar ellipticity = millidegree*molecular weight/(10*path length*concentration)). The subtracted milidegree means that the milidegree reported here has been baseline corrected.
UV-vis.xlsx
This file contains the raw UV-vis data for the most evolved variant. Measurement is taken at 1 mm path length, and absorbance is recorded at individual wavelengths (nm)
final_kinetic.xlsx
This file contains the kinetic data for the N2 evolution at different concentrations of the olefin substrate. N2 tab contains time vs N2 evolution in bar. All five conditions are included here, with the column clearly labeled. Five individual tabs contain the first derivative data. The first derivative plot is plotted by taking a moving average of 200 data points of every 10th data point to calculate the rate of the N2 generation (this is the description of the formula). For data points prior to the first 200 data points, the value is displayed as N/A. Plot fitting is applied when the trend is less apparent.
kinetic_2.xlsx
This file contains the kinetic data for the N2 evolution at different EDA concentrations. Also, N2 evolution in µmol is also included here. Four individual tabs contain the first derivative data for the 4 different EDA concentrations. The first derivative plot is plotted by taking a moving average of 200 data points of every 10th data point to calculate the rate of the N2 generation(this is the description of the formula). For data points prior to the first 200 data points, the value is displayed as N/A. Plot fitting is applied when the trend is less apparent. Max rate plot for the 4 different EDA concentrations is also included here as another tab. All time-point data here has been corrected to treat the point of injection as t0, and pressure has been corrected by subtracting the baseline pressure in the flask.
VCD_DFT_calc.txt
This file contains the DFT calculation for the VCD analysis