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Review

Design, Synthesis, and Utility of Defined Molecular Scaffolds

by 1,2,†, 2,†, 2,3,* and 2,*
1
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
2
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA
3
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
*
Authors to whom correspondence should be addressed.
Equal contributions by both authors.
Academic Editor: David StC Black
Received: 15 May 2021 / Accepted: 18 June 2021 / Published: 11 July 2021
(This article belongs to the Special Issue Feature Papers in Organics)
A growing theme in chemistry is the joining of multiple organic molecular building blocks to create functional molecules. Diverse derivatizable structures—here termed “scaffolds” comprised of “hubs”—provide the foundation for systematic covalent organization of a rich variety of building blocks. This review encompasses 30 tri- or tetra-armed molecular hubs (e.g., triazine, lysine, arenes, dyes) that are used directly or in combination to give linear, cyclic, or branched scaffolds. Each scaffold is categorized by graph theory into one of 31 trees to express the molecular connectivity and overall architecture. Rational chemistry with exacting numbers of derivatizable sites is emphasized. The incorporation of water-solubilization motifs, robust or self-immolative linkers, enzymatically cleavable groups and functional appendages affords immense (and often late-stage) diversification of the scaffolds. Altogether, 107 target molecules are reviewed along with 19 syntheses to illustrate the distinctive chemistries for creating and derivatizing scaffolds. The review covers the history of the field up through 2020, briefly touching on statistically derivatized carriers employed in immunology as counterpoints to the rationally assembled and derivatized scaffolds here, although most citations are from the past two decades. The scaffolds are used widely in fields ranging from pure chemistry to artificial photosynthesis and biomedical sciences. View Full-Text
Keywords: aqueous; functional molecule; graph; hub; peptide; rational synthesis; tree; triazine aqueous; functional molecule; graph; hub; peptide; rational synthesis; tree; triazine
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MDPI and ACS Style

Sato, D.; Wu, Z.; Fujita, H.; Lindsey, J.S. Design, Synthesis, and Utility of Defined Molecular Scaffolds. Organics 2021, 2, 161-273. https://0-doi-org.brum.beds.ac.uk/10.3390/org2030013

AMA Style

Sato D, Wu Z, Fujita H, Lindsey JS. Design, Synthesis, and Utility of Defined Molecular Scaffolds. Organics. 2021; 2(3):161-273. https://0-doi-org.brum.beds.ac.uk/10.3390/org2030013

Chicago/Turabian Style

Sato, Daisuke, Zhiyuan Wu, Hikaru Fujita, and Jonathan S. Lindsey 2021. "Design, Synthesis, and Utility of Defined Molecular Scaffolds" Organics 2, no. 3: 161-273. https://0-doi-org.brum.beds.ac.uk/10.3390/org2030013

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