This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Marine Furanocembranoids-Inspired Macrocycles Enabled by Pd-catalyzed Unactivated C(sp3)-H Insertion Reaction of Donor/Donor Carbenes
Weibo Yang
Shanghai Institute of Materia Medica
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1633-7655
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Biomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we unprecedentedly synthesized diverse alkenes substituted furan-embedded macrolactams via a modular biomimetic assembly strategy. The success of this assembly is the development of crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor carbene precursors and unactivated Csp3‒H bonds which represents a great challenge in organic synthesis. Notably, this method not only obviates the use of unstable, explosive, and toxic diazo compounds, but also can be amenable to allenyl ketones carbene precursors. DFT calculations demonstrated that a 1,4-Pd shift could be involved in the mechanism. Moreover, the collected furanocembranoids-like macrolactams showed significant anti-inflammatory activities against TNF-α, IL-6, and IL-1β and the low cytotoxicity is comparable to Dexamethasone.
Keywords
Biomimetic Modularization, Function Oriented Synthesis, Diazo Compounds, Allenyl Ketones Carbene Precursors, Dexamethosone
Figure 1
Figure 2
Figure 3
Due to technical limitations, full-text HTML conversion of the tables and schemes could not be completed. However, they can be downloaded and accessed in the Supplementary Files.
This is a list of supplementary files associated with this preprint. Click to download.
- supplement1.docx
Tables and Schemes
- supplement2.docx
Supporting information
- supplement3.cif
Dataset 1
- supplement4.cif
Dataset 2
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Under Review
Version 1
Posted 25 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint. It has not completed peer review.
Article
Marine Furanocembranoids-Inspired Macrocycles Enabled by Pd-catalyzed Unactivated C(sp3)-H Insertion Reaction of Donor/Donor Carbenes
Weibo Yang
Shanghai Institute of Materia Medica
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1633-7655
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Under Review
Version 1
Posted 25 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Biomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we unprecedentedly synthesized diverse alkenes substituted furan-embedded macrolactams via a modular biomimetic assembly strategy. The success of this assembly is the development of crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor carbene precursors and unactivated Csp3‒H bonds which represents a great challenge in organic synthesis. Notably, this method not only obviates the use of unstable, explosive, and toxic diazo compounds, but also can be amenable to allenyl ketones carbene precursors. DFT calculations demonstrated that a 1,4-Pd shift could be involved in the mechanism. Moreover, the collected furanocembranoids-like macrolactams showed significant anti-inflammatory activities against TNF-α, IL-6, and IL-1β and the low cytotoxicity is comparable to Dexamethasone.
Figure 1
Figure 2
Figure 3
Due to technical limitations, full-text HTML conversion of the tables and schemes could not be completed. However, they can be downloaded and accessed in the Supplementary Files.