Multifunctional Dendrimer Formation Using Thiolactone Chemistry

Abstract

Thiolactone chemistry is a powerful tool for the design of complex multifunctional architectures. In this study, this versatile click-inspired synthetic strategy is conducted to prepare multifunctional dendrimer-like structures. For this purpose, a thiolactone bearing an isocyanate function, prepared in multigram scale, is utilized for multiple step functionalization starting from a 4-arm star-shaped poly(ethylene glycol). Amine-thiol-acrylate conjugation is carried out in order to form the aforementioned structures. The efficient aminolysis of the thiolactone ring and the reaction of the generated thiol with the double bond of an acrylate derivative are completed in a one-pot procedure. The choice of the amine and/or acrylate derivatives can allow the introduction of different functional groups for each new gene ration, potentially leading to multivalent dendrimer-like structures.

Synthesis, structure, and function of internally functionalized dendrimers

“…An IFD functionalized with butyl ester or the nonlinear optical chromophore Dispersed Red 1 distributed along its backbone was reported by Kaya et al 123 The synthetic pathway hinges on thiolactone chemistry for efficient and simple reaction ( Figure 15): (i) a four arm PEG core with terminal hydroxyl groups was initially exposed to thiolactone isocyanate to provide the thiolactone-terminated intermediate (A); a one-pot reaction was then performed on (A) using (ii) N-(3-aminopropyl)diethanolamine to amidate the thiolactone and (iii) an acrylate monomer displaying the desired functionality via thiol-Michael addition to the generated thiol group (note: in this work, the authors employed either nbutyl acrylate or Disperse Red 1 acrylate), resulting in the dendrimer intermediate (B). The sequence was repeated to furnish IFD's up to generation 3.…”

“…IFD displaying either butyl ester or dispersed red 1 functionalities as prepared by Kaya et al 123 IFD, internally functionalized dendrimers…”

A sequential native chemical ligation – thiol-Michael addition strategy for polymer–polymer ligation

“…The latent thiol functionality has been exploited for thiol-Michael additional, 14 radical thiol-ene 13 /yne 15 and disulfide bond formation. 16 The strategy has been employed for sequencedefined oligomer synthesis 17 and construction of dendrimers, 18 using iterative step-growth protocols, while thiolactone functional reagents for RDRP have also been synthesised providing access to functional polymer scaffolds. 19 A much less regarded reaction in polymer science is native chemical ligation (NCL), which is frequently employed for the synthesis of peptides and proteins.…”

Scope and Limitations of Xanthate-Mediated Synthesis of Functional γ-Thiolactones

“…They highlighted that amines could readily open γ-thiolactones to generate a thiol that could be further reacted with a reactive double bond in a one-pot procedure. 10,11 The use of various functionalized homocysteine thiolactones for this so-called amine–thiol–ene conjugation reaction has led to the synthesis of a tremendous amount of complex functional polymers, 11,12 some exhibiting sequence-controlled structures. 13−17 Although this new reaction in polymer synthesis seems really promising, the modified homocysteine thiolactones available show a relatively limited structural diversity, with the amine group as the only possible substitution site.…”