3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors
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 lab...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/18/9919 |
_version_ | 1797518900767752192 |
---|---|
author | Kirill S. Erokhin Evgeniy G. Gordeev Dmitriy E. Samoylenko Konstantin S. Rodygin Valentine P. Ananikov |
author_facet | Kirill S. Erokhin Evgeniy G. Gordeev Dmitriy E. Samoylenko Konstantin S. Rodygin Valentine P. Ananikov |
author_sort | Kirill S. Erokhin |
collection | DOAJ |
description | 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 (C<sub>2</sub>H<sub>2</sub>, H<sub>2</sub>, C<sub>2</sub>D<sub>2</sub>, D<sub>2</sub>, and CO<sub>2</sub>) 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 (C<sub>2</sub>D<sub>2</sub>) and deuterium gas (D<sub>2</sub>), 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. |
first_indexed | 2024-03-10T07:35:50Z |
format | Article |
id | doaj.art-812b32f9909545028cbe22053fbd5d74 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T07:35:50Z |
publishDate | 2021-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-812b32f9909545028cbe22053fbd5d742023-11-22T13:29:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218991910.3390/ijms221899193D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation ReactorsKirill S. Erokhin0Evgeniy G. Gordeev1Dmitriy E. Samoylenko2Konstantin S. Rodygin3Valentine P. Ananikov4N. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, RussiaN. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, RussiaInstitute of Chemistry, Saint Petersburg State University, Universitetsky Prospect 26, 198504 Peterhof, RussiaN. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, RussiaN. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, RussiaThe 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 (C<sub>2</sub>H<sub>2</sub>, H<sub>2</sub>, C<sub>2</sub>D<sub>2</sub>, D<sub>2</sub>, and CO<sub>2</sub>) 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 (C<sub>2</sub>D<sub>2</sub>) and deuterium gas (D<sub>2</sub>), 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.https://www.mdpi.com/1422-0067/22/18/99193D printingadditive manufacturingacetylenecarbon dioxidehydrogenorganic synthesis |
spellingShingle | Kirill S. Erokhin Evgeniy G. Gordeev Dmitriy E. Samoylenko Konstantin S. Rodygin Valentine P. Ananikov 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors International Journal of Molecular Sciences 3D printing additive manufacturing acetylene carbon dioxide hydrogen organic synthesis |
title | 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors |
title_full | 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors |
title_fullStr | 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors |
title_full_unstemmed | 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors |
title_short | 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors |
title_sort | 3d printing to increase the flexibility of the chemical synthesis of biologically active molecules design of on demand gas generation reactors |
topic | 3D printing additive manufacturing acetylene carbon dioxide hydrogen organic synthesis |
url | https://www.mdpi.com/1422-0067/22/18/9919 |
work_keys_str_mv | AT kirillserokhin 3dprintingtoincreasetheflexibilityofthechemicalsynthesisofbiologicallyactivemoleculesdesignofondemandgasgenerationreactors AT evgeniyggordeev 3dprintingtoincreasetheflexibilityofthechemicalsynthesisofbiologicallyactivemoleculesdesignofondemandgasgenerationreactors AT dmitriyesamoylenko 3dprintingtoincreasetheflexibilityofthechemicalsynthesisofbiologicallyactivemoleculesdesignofondemandgasgenerationreactors AT konstantinsrodygin 3dprintingtoincreasetheflexibilityofthechemicalsynthesisofbiologicallyactivemoleculesdesignofondemandgasgenerationreactors AT valentinepananikov 3dprintingtoincreasetheflexibilityofthechemicalsynthesisofbiologicallyactivemoleculesdesignofondemandgasgenerationreactors |