TY - JOUR

T1 - 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors

AU - Erokhin, Kirill S.

AU - Gordeev, Evgeniy G.

AU - Samoylenko, Dmitriy E.

AU - Rodygin, Konstantin S.

AU - Ananikov, Valentine P.

N1 - Erokhin, K.S.; Gordeev, E.G.; Samoylenko, D.E.; Rodygin, K.S.; Ananikov, V.P. 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors. Int. J. Mol. Sci. 2021, 22, 9919. https://doi.org/10.3390/ijms22189919

PY - 2021/9

Y1 - 2021/9

N2 - The development of new drugs is accelerated by rapid access to functionalized and D-labeled molecules with improved activity and pharmacokinetic profiles. Diverse synthetic procedures often involve the usage of gaseous reagents, which can be a difficult task due to the requirement of a dedicated laboratory setup. Here, we developed a special reactor for the on-demand production of gases actively utilized in organic synthesis (C2H2, H2, C2D2, D2, and CO2) that completely eliminates the need for high-pressure equipment and allows for integrating gas generation into advanced laboratory practice. The reactor was developed by computer-aided design and manufactured using a conventional 3D printer with polypropylene and nylon filled with carbon fibers as materials. The implementation of the reactor was demonstrated in representative reactions with acetylene, such as atom-economic nucleophilic addition (conversions of 19-99%) and nickel-catalyzed S-functionalization (yields 74-99%). One of the most important advantages of the reactor is the ability to generate deuterated acetylene (C2D2) and deuterium gas (D2), which was used for highly significant, atom-economic and cost-efficient deuterium labeling of S,O-vinyl derivatives (yield 68-94%). Successful examples of their use in organic synthesis are provided to synthesize building blocks of heteroatom-functionalized and D-labeled biologically active organic molecules.

AB - The development of new drugs is accelerated by rapid access to functionalized and D-labeled molecules with improved activity and pharmacokinetic profiles. Diverse synthetic procedures often involve the usage of gaseous reagents, which can be a difficult task due to the requirement of a dedicated laboratory setup. Here, we developed a special reactor for the on-demand production of gases actively utilized in organic synthesis (C2H2, H2, C2D2, D2, and CO2) that completely eliminates the need for high-pressure equipment and allows for integrating gas generation into advanced laboratory practice. The reactor was developed by computer-aided design and manufactured using a conventional 3D printer with polypropylene and nylon filled with carbon fibers as materials. The implementation of the reactor was demonstrated in representative reactions with acetylene, such as atom-economic nucleophilic addition (conversions of 19-99%) and nickel-catalyzed S-functionalization (yields 74-99%). One of the most important advantages of the reactor is the ability to generate deuterated acetylene (C2D2) and deuterium gas (D2), which was used for highly significant, atom-economic and cost-efficient deuterium labeling of S,O-vinyl derivatives (yield 68-94%). Successful examples of their use in organic synthesis are provided to synthesize building blocks of heteroatom-functionalized and D-labeled biologically active organic molecules.

KW - 3D printing

KW - Additive manufacturing

KW - Acetylene

KW - Carbon dioxide

KW - Hydrogen

KW - Organic synthesis

KW - 3D printing

KW - additive manufacturing

KW - acetylene

KW - carbon dioxide

KW - hydrogen

KW - Organic synthesis

UR - http://www.scopus.com/inward/record.url?scp=85115113869&partnerID=8YFLogxK

U2 - 10.3390/ijms22189919

DO - 10.3390/ijms22189919

M3 - Article

C2 - 34576082

AN - SCOPUS:85115113869

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 18

M1 - 9919

ER -