A short synthesis of siloxane phosphocholines

Abstract

Herein, we report our first generation synthesis of two new silicon‐containing phosphocholines (SiPCs) in which the fatty acid chains are terminated by trisiloxane units. We have been exploring the limits to which immobilized lipases can be used in the field of organosilicon chemistry, and the cornerstone of this work is a chemoenzymatic approach to synthesizing SiPCs that are structurally analogous to naturally occurring species such as 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC). Practical applications: This research focuses on the chemoenzymatic synthesis of siloxane‐containing phospholipid systems. These compounds have different surface properties than the comparable biologically relevant phospholipids opening the doors for the potential application of these siloxane‐containing species as encapsulation/delivery vehicles and as a means of modifying surfaces. Surface pressure‐molecular area isotherms for siloxane‐phospholipids.

A Flexible Synthetic Approach to Phosphatidylglycerols

“…Major differences observed in 1 H and 31 P NMR spectra of the two separated esterification products (i.e. desired 11a – f and the corresponding impurity) correlate to reported NMR spectra differences of silicon containing 1,2‐ and 1,3‐diacyl‐PC and of 1,2‐ and 1,3‐diacyl phosphatidic acid derivatives . So far, a 20 to 30 % phosphoryl migration (from sn ‐3 to sn ‐2 position of the central glycerol) occurring during the benzylation reaction is the most credible explanation for the presence of the impurity.…”

Biocatalysis in Silicon Chemistry

“…Frampton et al [114] examined the surface area-pressure isotherms of these new lipids, as well as those of 1,2-dipalmitoylsn-3-glycerophosphocholine (DPPC) and 1-palmitoyl-2-oleoylsn-3-glycerophosphocholine (POPC), to characterize the approximate area/lipid and the behavior of monolayer films. The cross-sectional surface area of these lipids at collapse was 70 and 87 2 for the 1,2-and 1,3-substituted lipids, respectively.…”

“…Attempts to produce these macrolactones by incorporating 1,2cyclohexanediol into the macrocyclic structurew ere unsuccessful. The success of this approach was heavily dependent on the chain length of the ester;atheme that hasbeen reinforced throughout work by Zelisko [83,84,91,97,108,114] on enzymatic polymerizationsofs iloxanes.…”

“…Over the years, we had been intrigued by the notion of incorporatings ilicon-containing groups into biomolecules such as amino acids and phospholipids.T he hydrophobic nature of siloxanes shouldc omplementt he hydrophobic nature of the fatty acids of phospholipids;h owever,w hen Zelisko and coworkers [114] started to design ap rogram around such structures, there was only one report in the literatureinw hich siloxanes had been appended to the fatty acid chains.K allury et al prepared two silicon-containing phosphocholines, in which one of the chains was modified with ac hlorodimethylsiloxy group to facilitate the functionalization of silicon wafers. [110] Since 1987, there had been reports of non-phospholipids bearing trialkoxysilyl moieties in the head group of the lipids, for which the end goal was the synthesis of bicelles and crosslinked cerasomes.…”

“…[111][112][113] Frampton and Zelisko reported their first-generation synthesis of siloxane-containing phosphocholines in 2016, which featured a Rhizomucor miehei lipase (Lipozyme RM)-mediated double esterification of glycerol with as iloxane fatty acid to give am ixture of diacylglycerides ( Figure 22). [114] The authors chose this particular enzymeo ver more commonly used N435 because the latter enzyme produced large amounts of the triacyl glyceride at the expense of the desired diacyl glyceride. Although LipozymeRMhas sn-1,3 selectivity, Frampton and Zelisko recovered considerable amounts of the 1,2-diacyl glyceride, which resulted from acyl migration;aserendipitousr esult that allowed the synthesis of two differentp hospholipids.…”