Abstract
Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron’s focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron’s azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization.
Highlights
IntroductionDendritic polymers based on 2,2-bis(methylol)propionic acid (bis-MPA) belong to one of the most established families of dendritic polymers and were introduced by Hult et al in the 1990s [1,2]
Dendritic polymers based on 2,2-bis(methylol)propionic acid belong to one of the most established families of dendritic polymers and were introduced by Hult et al in the 1990s [1,2].These commercially available scaffolds are biodegradable and biocompatible [3], with long shelf-life and simple synthetic protocols and they fulfill all the necessary criteria for future technological breakthroughs in the field of biomedicine
An example is the limited yields achieved during the convergent synthesis of bis(methylol)propionic acid (bis-MPA) dendrimers from higher generation dendrons
Summary
Dendritic polymers based on 2,2-bis(methylol)propionic acid (bis-MPA) belong to one of the most established families of dendritic polymers and were introduced by Hult et al in the 1990s [1,2]. These commercially available scaffolds are biodegradable and biocompatible [3], with long shelf-life and simple synthetic protocols and they fulfill all the necessary criteria for future technological breakthroughs in the field of biomedicine. The exceptional structural perfection of bis-MPA dendrimers have resulted in state-of-the-art MALDI-MS calibrants, SpheriCal® , that outperform current peptide and protein based standards [18].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
