A Scalable and Versatile Synthesis of Oxime‐Based Hormone Dimers and Gels for Sustained Release

Abstract

Well-defined steroid hormone dimers and organogels were produced via af acile and scalables ynthesis using oxime click chemistry.T he versatile synthetic procedure extends to aw ide range of hormones and linker groups exemplified here through the synthesis of cortisoland progesterone-dimers linked via hydrophobic, hydrophilic or functional groups. This method was also extended to the synthesis of cortisone-based organogels. Owing to the dynamic nature of the oxime bond, the hormonebased materials are degradable via acidic hydrolysis and transoximination representing new materials for the controlled releaseo fs teroid hormones.

Tunable degradation of polyethylene glycol‐like polymers based on imine and oxime bonds

“…Additionally, characteristic peaks confirming progesterone conjugation were identified. As previously reported, under mild conditions, oxime formation on progesterone occurs only at the C3 ketone site and causes a characteristic splitting of the adjacent H4 proton peak into two singlet peaks caused by the formation of the two oxime isomers ( E and Z ) . This is observed in the 1 H‐NMR spectra of PEG ox‐Prog in which the H4 peak of progesterone is split from a singlet at 5.73 ppm into two singlets at 5.74 and 6.41 ppm indicating successful oxime formation at the C3 ketone site (Fig.…”

“…As previously reported, under mild conditions, oxime formation on progesterone occurs only at the C3 ketone site and causes a characteristic splitting of the adjacent H4 proton peak into two singlet peaks caused by the formation of the two oxime isomers (E and Z). 35,37 This is observed in the 1 H-NMR FIGURE 2 Polymer degradation at pH 7.4 recorded over 5 days. Polymer molecular weights, measured via GPC and calculated relative to PEG standards, are recorded as a percentage of original mass.…”

“…We identified progesterone as a representative drug‐like molecule to demonstrate the ability to prepare drug‐ PEG ox conjugates for potential applications in drug delivery. Previously, progesterone has been reported to be functionalized with small molecules due to the accessible carbonyl bonds that can react with hydroxylamines . Successful conjugation of progesterone to a hydroxylamine‐terminated PEG ox allowed for the preparation of PEG ox ‐progesterone conjugates ( PEG ox‐Prog ).…”

“…Previously, progesterone has been reported to be functionalized with small molecules due to the accessible carbonyl bonds that can react with hydroxylamines. [35][36][37] Successful conjugation of progesterone to a hydroxylamine-terminated PEG ox allowed for the preparation of PEG ox -progesterone conjugates (PEG ox-Prog ).…”

A review on steroid dimers: 2011–2019

“…Four cortisol and progesterone-based dimers 109-112 were synthesized using oxime click chemistry linked via hydrophobic, hydrophilic or functional groups, and because of the dynamic nature of the oxime bonds, the steroid-based materials are degradable via acidic hydrolysis and transoximination, potentially making these oxime-based dimers a promising group of materials for the controlled or sustained release steroid hormonal formulations [19]…”