Automated Synthesis Facility

Equipment for reaction setup:

• Unchained Labs Freeslate robotic platform with liquid handling, solid dispense, mixing, temperature control, filtration, and pressure capabilities, housed in a nitrogen purge box
• Unchained Labs Freeslate Jr with OSR robotic platform with parallel pressure reactors with overhead stirring, independent temperature control, independent pressure control, and the ability to add reagents and remove reaction aliquots while under pressure, housed in a nitrogen purge box
• ThermoFisher plate SpeedVac, housed in the same nitrogen purge box as the Freeslate robotic platform
• V&P Scientific tumble stirrer with independent heating zones, not in purge box

• Biotage Initiator+ Alstra microwave peptide synthesizer

• Triton centrifugal peptide synthesizer

Equipment for analysis:

• Waters I-Class LC with diode array and G2-XS time of flight (TOF) mass spec
• Waters I-Class LC with diode array and SQD2 mass spec
• Waters I-Class LC with diode array and QDa mass spec (x2)
• Waters H-Class LC with diode array and QDa mass spec
• Waters I-Class LC with diode array
• Waters UPC2 SFC with diode array, QDa mass spec, and chiral columns
• Waters heartcutting 2D LC-SFC (combination of above two instruments)
• Advion TLC-MS (x2)

• Mettler-Toledo Autochem ReactIR 15

Equipment for purification:

• Waters Autopurify prep LC with diode array and QDa mass spec

• Waters 150 AP prep SFC with diode array and QDa mass spec, with chiral and achiral columns 

Key software:

• Reaction planning: Library Studio (Unchained Labs)

• Data processing: Empower (Waters), MassLynx (Waters), MassWorks (Cerno Bioscience)

• Data visualization: Spotfire (TIBCO)

K. Simlandy, T. M. alturaifi, J. M. Nguyen, L. J. Oxtoby, Q. N. Wong, J. S. Chen, P. Liu, K. M. Engle, “Enantioselective hydroalkeylation and hydroalkynylation of alkenes enabled by a transient directing group: Catalyst generality through rigidification,” Angew. Chem. Int. Ed. 2023, 62, e202304013.

T. Tran, N. Kim, C. Z. Rubel, X. Wu, T. Kang, T. C. Jankins, Z.-Q. Li, W. V. Joannou, S. Ayers, M. Gembicky, J. Baily, E. J. Sturgell, B. B. Sanchez, J. S. Chen, S. Lin, M. D. Eastgate, S. R. Wisniewski, K. M. Engle, “Structurally diverse bench-stable nickel(0) pre-catalysts: A practical toolkit for in situ ligation protocols,” Angew. Chem. Int. Ed. 2023, 62, e202211794.

Apolinar, T. Kang, T. M. Alturaifi, P. G. Bedekar, C. Z. Rubel, J. Derosa, B. B. Sanchez, Q. N. Wong, E. J. Sturgell, J. S. Chen, S. R. Wisniewski, P. Liu, K. M. Engle, “Three-component asymmetric Ni-catalyzed 1,2-dicarbofunctionalization of unactivated alkenes via stereoselective migratory insertion,” J. Am. Chem. Soc. 2022, 144, 19337 – 19343.

 Hao, C. L. Joe, A. Darù, S. Ayers, A. Ramirez, B. Sandhu, R. A. Daley, J. S. Chen, M. A. Schmidt, D. G. Blackmond, “Kinetic and thermodynamic considerations in the Rh-catalyzed enantioselective hydrogenation of 2-pyridyl-substituted alkenes,” ACS Catal. 2022, 12, 5961 – 5969.

-C. Lin, F. Schneider, K. J. Eberle, D. Chiodi, H. Nakamura, S. H. Reisberg, J. Chen, M. Saito, P. S. Baran, “Atropselective total synthesis of darobactin A,” J. Am. Chem. Soc. 2022, 144, 14458 – 14462.

He, Y. Wang, C. Bi, D. S. Peters, T. J. Gallagher, J. Teske, J. S. Chen, R. Corsetti, A. D’Onofrio, K. Lewis, P. S. Baran, “Total synthesis of kibdelomycin,” Angew. Chem. Int. Ed., 2022, 61, e20226183. 

Gu, K. X. Rodriguez, Y. Kanda, S. Yang, M. Ociepa, H. Wilke, A. V. Abrishami, L. Jørgensen, T. Shak-Nielsen, J. S. Chen, P. S. Baran, “Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs,” Proc. Natl. Acad. Sci. 2022, 119, e2200814119.

C. Jankins, W. C. Bell, Y. Zhang, Z.-Y. Qin, J. S. Chen, M. Gembicky, P. Liu, K. M. Engle, “Low-valent tungsten redox catalysis enables controlled isomerization and carbonylative functionalization of alkenes,” Nature Chem. 2022, 14, 632 – 639.

Hao, C. L. Joe, S. Ayers, A. Darù, R. A. Daley, M. Domanski, J. S. Chen, M. A. Schmidt, D. G. Blackmond, “Ru-catalyzed enantioselective hydrogenation of 2-pyridyl-substituted alkenes and substrate-mediated H/D exchange,” ACS Catal. 2022, 12, 1150 – 1160.

G. Saint-Denis, N. Y. S. Lam, N. Chekshin, P. F. Richardson, J. S. Chen, J. Elleraas, K. D. Hesp, D. C. Schmitt, Y. Lian, C. W. Huh, J.-Q. Yu, “Mechanistic study of enantioselective Pd-catalyzed C(sp³)–H activation of thioethers involving two distinct stereomodels,” ACS Catal. 2021, 11, 9738 – 9753.

Ociepa, K. W. Knouse, D. He, J. C. Vantourout, D. T. Flood, N. M. Padial, J. S. Chen, B. B. Sanchez, E. J. Sturgell, B. Zheng, S. Qiu, M. A. Schmidt, M. D. Eastgate, P. S. Baran, “Mild and chemoselective phosphorylation of alcohols using a Y-reagent,” Org. Lett. 2021, 23, 9337 – 9342.

L. D. Turner, A. L. Nielsen, L. Lin, A. J. Campedelli, N. R. Silvaggi, J. S. Chen, A. E. Wakefield, K. N. Allen, K. D. Janda, “Use of crystallography and molecular modeling for the inhibition of the botulinum neurotoxin A protease,” ACS Med. Chem. Lett. 2021, 12, 1318 – 1324. 

D. A. Dik, N. Zhang, E. J. Sturgell, B. B. Sanchez, J. S. Chen, B. Webb, K. G. Vanderpool, P. G. Schultz, “A synthetic 5,3-cross-link in the cell wall of rod-shaped Gram-positive bacteria,” Proc. Natl. Acad. Sci. 2021, 118, e2100137118.

D. T. Flood, J. C. J. Hintzen, K. W. Knouse, D. E. Hill, C. Lu, P. A. Cistrone, J. S. Chen, T. Otomo, P. E. Dawson, “Selenomethionine as an expressible handle for bioconjugations,” Proc. Natl. Acad. Sci. 2021, 118, e2005164118

D. T. Flood, K. W. Knouse, J. C. Vantourout, S. Kitamura, B. B. Sanchez, E. J. Sturgell, J. S. Chen, D. W. Wolan, P. S. Baran, P. E. Dawson, “Synthetic elaboration of native DNA by RASS (SENDR),” ACS Central Sci. 2020, 6, 1789 – 1799.

Z. Fan, S. Zhao, T. Liu, P.-X. Shen, Z.-N. Cui, Z. Zhuang, Q. Shao, J. S. Chen, A. S. Ratnayake, M. E. Flanagan, D. K. Kölmel, D. W. Piotrowski, P. Richardson, J.-Q. Yu, “Merging C(sp³)-H activation with DNA-encoding,” Chem. Sci. 2020, 11, 12282 – 12288.

N. Yan, D. Santos-Martins, E. Rennella, B. B. Sanchez, J. S. Chen, L. E. Kay, I. A. Wilson, G. J. Morgan, S. Forli, J. W. Kelly, “Structural basis for the stabilization of amyloidogenic immunoglobin light chains by hydantoins,” Bioorg. Med. Chem. Lett. 2020, 30, article 127356. 

A. X. Jones, L. Wen, L. Legnani, J. Chen, D. G. Blackmond, “Asymmetric amplification in peptide-catalyzed formation of tetrose sugars from nearly racemic amino acids,” J. Systems Chem. 2020, 8, 63 - 72.

D. A. Dik, N. Zhang, J. S. Chen, B. Webb, P. G. Schultz, “Semi-synthesis of a bacterium with non-canonical cell wall crosslinks,” J. Am. Chem. Soc. 2020, 142, 10910 – 10913.

C. Zambaldo, E. V. Vinogradova, X. Qi, J. Iaconelli, R. M. Suciu, M. Koh, K. Senkane, S. R. Chadwick, B. B. Sanchez, J. S. Chen, A. K. Chatterjee, P. Liu, P. G. Schultz, B. F. Cravatt, M. J. Bollong, “2-Sulfonyl pyridines as tunable, cysteine-reactive electophiles,” J. Am. Chem. Soc., 2020, 142, 8972 – 8979.

S. Qian, Z.-Q. Li, M. Li, S. R. Wisniewski, J. X. Qiao, J. M. Richter, W. R. Ewing, M. D. Eastgate, J. S. Chen, J.-Q. Yu, “Ligand-enabled Pd(II)-catalyzed C(sp3)–H lactonization using molecular oxygen as oxidant,” Org. Lett. 2020, 22, 3960 – 3963.

J. L. M. Matos, S. A. Green, Y. Chun, V. Q. Dang, R. G. Dushin, P. Richardson, J. S. Chen, D. W. Piotrowski, B. M. Paegel, R. A. Shenvi, “Cycloisomerization of olefins in water,” Angew. Chem. Int. Ed., 2020, 59, 12998 – 13003

D. T. Flood, X. Zhang, X. Fu, Z. Zhao, S. Asai, B. B. Sanchez, E. J. Sturgell, J. C. Vantourout, P. Richardson, M. E. Flanagan, D. W. Piotrowski, D. K. Kölmel, J. Wan, M.-H. Tsai, J. S. Chen, P. Baran, P. E. Dawson, “RASS-enabled S/P–C and S–N bond formation for DEL synthesis,” Angew. Chem. Int. Ed. 2020, 59, 7377 – 7383.

D.-W. Gao, Y. Gao, H. Shao, T.-Z. Qiao, X. Wang, B. B. Sanchez, J. S. Chen, P. Liu, K. M. Engle, “Cascade CuH-catalyzed conversion of alkynes to enantioenriched 1,1-disubstituted products,” Nature Catal. 2020, 3, 23 – 29.

A. M. Romine, K. S. Yang, M. K. Karunananda, J. S. Chen, K. M. Engle, “Synthesis and mechanistic studies of a versatile heteroaryl thioether directing group for Pd(II) catalysis,” ACS Catal. 2019, 9, 7626 – 7640.

A. W. Feldman, V. T. Dien, R. J. Karadeema, E. C. Fischer, Y. You, B. A. Anderson, R. Krishnamurthy, J. S. Chen, L. Li, F. E. Romesberg, “Optimization of replication, transcription, and translation in a semi-synthetic organism,” J. Am. Chem. Soc. 2019, 141, 10644 – 10653.

D. T. Flood, S. Asai, X. Zhang, J. Wang, L. Yoon, Z. C. Adams, B. C. Dillingham, B. B. Sanchez, J. C. Vantourout, M. E. Flanagan, D. W. Piotrowski, P. Richardson, S. A. Green, R. A. Shenvi, J. S. Chen, P. S. Baran, P. E. Dawson, “Expanding reactivity in DNA-encoded library synthesis via reversible binding of DNA to an inert quaternary ammonium support,” J. Am. Chem. Soc. 2019 , 141, 9998 – 10006.

S. Ni, N. M. Padial, C. Kingston, J. C. Vantourout, D. C. Schmitt, J. T. Edwards, M. M. Kruszyk, R. R. Merchant, P. K. Mykhailiuk, B. B. Sanchez, S. Yang, M. A. Perry, G. M. Gallego, J. J. Mousseau, M. R. Collins, R. J. Cherney, P. S. Lebed, J. S. Chen, T. Qin, P. S. Baran, “A radical approach to anionic chemistry: Synthesis of ketones, alcohols, and amines,” J. Am. Chem. Soc. 2019 , 141, 6726 – 6739.

S. K. Nimmagadda, M. Liu, M. K. Karunananda, D.-W. Gao, O. Apolinar, J. S. Chen, P. Liu, K. M. Engle, “Catalytic, enantioselective α-alkylation of azlactones with nonconjugated alkenes by directed nucleopalladation,” Angew. Chem., Int. Ed. 2019, 58, 3923 – 3927.

C. Kingston, M. A. Wallace, A. J. Allentoff, J. N. deGruyter, J. S. Chen, S. X. Gong, S. Bonacorsi, Jr., P. S. Baran, “Direct carbon isotope exchange through decarboxylative carboxylation,” J. Am. Chem. Soc. 2019, 141, 774 – 779.

D. T. Flood, J. C. J. Hintzen, M. J. Bird, P. A. Cistrone, J. S. Chen, P. E. Dawson, “Leveraging the Knorr pyrazole synthesis for the facile generation of thioester surrogates for use in native chemical ligation,” Angew. Chem., Int. Ed. 2018 , 57, 11634 – 11639.

T.-G. Chen, L. M. Barton, Y. Lin, J. Tsien, D. Kossler, I. Bastida, S. Asai, C. Bi, J. S. Chen, M. Shan, H. Fang, F. G. Fang, H.-w. Choi, L. Hawkins, T. Qin, P. S. Baran, “Building C(sp ³)-rich complexity by combining cycloaddition and C–C cross-coupling reactions,” Nature 2018 , 560, 350 – 354.

J. Wang, H. Lundberg, S. Asai, P. Martin-Acosta, J. S. Chen, S. Brown, W. Farrell, R. Dushin, C. J. O’Donnell, A. S. Ratnayake, P. Richardson, Z. Liu, T. Qin, D. G. Blackmond, P. S. Baran, “Kinetically guided radical-based synthesis of C(sp3)–C(sp3) linkages on DNA,” Proc. Natl. Acad. Sci. 2018 , 115, E6404 – E6410 .

D.-W. Gao, Y. Xiao, M. Liu, Z. Liu, M. K. Karunananda, J. S. Chen, K. M. Engle, “Catalytic, enantioselective synthesis of allenyl boronates,” ACS Catal. 2018 , 8, 3650 – 3654.

J. Derosa, V. T. Tran, M. N. Boulous, J. S. Chen, K. M. Engle, “Nickel-catalyzed β,γ-dicarbofunctionalization of alkenyl carbonyl compounds via conjunctive cross-coupling,” J. Am. Chem. Soc. 2017 , 139, 10657 – 10660.