Synthesis of sulfur-containing precursor of targeted lipoconjugates

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Objectives: To search for and develop a method for synthesizing sulfur-containing lipids based on 1,2-di-O-tetradecyl-rac-glycerol. Methods. Separation and purification of the obtained compounds were accomplished by column chromatography on silica gel and extraction. A combination of physicochemical analytical methods, including NMR-spectroscopy and mass-spectrometry, was used to confirm the structures of the obtained compounds. Results. A new method for synthesizing sulfur-containing precursors for targeted lipoconjugates has been developed. 1,2-di-O-tetradecyl-rac-glycerol with a tetraethylene glycol spacer was used as the hydrophobic domain. Divinyl sulfone was attached to the terminal amino group under basic conditions. However, proton signals from the dioxothiomorphonyl group were detected in the NMR spectra of the resulting compound, confirming the cyclization of the vinylsulfone group with primary amines. This problem can be solved by replacing divinyl sulfone with its analog with an ethylene glycol spacer, bis-vinylsulfone, and alkylating the primary amino group of the tetraethylene glycol spacer, since the formation of the dioxothiomorphonyl group is excluded from secondary amines. Conclusions. The interaction of divinyl sulfone with the primary amino group of a tetraethyleneglycol-containing lipid based on 1,2-di-O-tetradecyl-rac-glycerol was investigated. The resulting addition reaction product was further used to create CL and study the delivery of NAto target cells. The search for optimal synthesis conditions for producing vinyl sulfone-containing precursors of the targeted lipoconjugates will also continue.

About the authors

V. М Lipenskiy

Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological University

Email: lipenskiy.v.m@gmail.com
ORCID iD: 0000-0002-3426-4915

E. V Shmendel

Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological University

ORCID iD: 0000-0003-3727-4905

M. A Maslov

Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological University

ORCID iD: 0000-0002-5372-1325

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