A Flexible Synthetic Approach to Phosphatidylglycerols

Gagnon, Marie‐Claude; Dautrey, Sébastien; Bertrand, Xavier; Auger, Michèle; Paquin, Jean‐François

doi:10.1002/ejoc.201701178

“…The benzylidene/ benzyl protecting groups were chosen for this synthesis due to the fact that they can be removed under hydrogenation conditions at the end of the synthesis, inhibiting phosphate migration that is observed under acidic or basic conditions. [43,44] The synthesized lipids were converted to boronic esters containing a chiral appendage (Scheme S1) and analyzed by using 31 P NMR. [45] No erosion of the stereochemical purity at the headgroup of PG could be detected (Figure S9).…”

mentioning

confidence: 99%

The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol

Moreira

¹

,

Taylor

²

2021

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Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium‐dependent manner. The enantiomer of dap (ent‐dap) was synthesized and was found to be 85‐fold less active than dap against B. subtilis, indicating that dap interacts with a chiral target as part of its mechanism of action. Using liposomes containing enantiopure PG, we demonstrate that the binding of dap to PG, the structural transition that occurs upon dap binding to PG, and the subsequent oligomerization of dap, depends upon the configuration of PG, and that dap prefers the 1,2‐diacyl‐sn‐glycero‐3‐phospho‐1′‐sn‐glycerol stereoisomer (2R,2′S configuration). Ent‐dap has a lower affinity for 2R,2′S liposomes than dap and cannot oligomerize to the same extent as dap, which accounts for why ent‐dap is less active than dap. To our knowledge, this is the first example whereby the activity of an antibiotic depends upon the configuration of a lipid head group.

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“…Removal of the benzyl and benzylidene protecting groups in 12 via hydrogenolysis followed by conversion of the resulting acids to their sodium salts and lyophilization provided all four stereoisomers of dimyristoylPG (DMPG) as white powders. The benzylidene/benzyl protecting groups were chosen for this synthesis due to the fact that they can be removed under hydrogenation conditions at the end of the synthesis, inhibiting phosphate migration that is observed under acidic or basic conditions [43, 44] . The synthesized lipids were converted to boronic esters containing a chiral appendage (Scheme S1) and analyzed by using 31 P NMR [45] .…”

Section: Figurementioning

confidence: 99%

The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol

Moreira

¹

,

Taylor

²

2021

View full text Add to dashboard Cite

Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium‐dependent manner. The enantiomer of dap (ent‐dap) was synthesized and was found to be 85‐fold less active than dap against B. subtilis, indicating that dap interacts with a chiral target as part of its mechanism of action. Using liposomes containing enantiopure PG, we demonstrate that the binding of dap to PG, the structural transition that occurs upon dap binding to PG, and the subsequent oligomerization of dap, depends upon the configuration of PG, and that dap prefers the 1,2‐diacyl‐sn‐glycero‐3‐phospho‐1′‐sn‐glycerol stereoisomer (2R,2′S configuration). Ent‐dap has a lower affinity for 2R,2′S liposomes than dap and cannot oligomerize to the same extent as dap, which accounts for why ent‐dap is less active than dap. To our knowledge, this is the first example whereby the activity of an antibiotic depends upon the configuration of a lipid head group.

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“…Therefore, all these compounds have a great commercial value in the food, pharmaceutical and cosmetic industry, especially in relation with the purity of the products. Their preparation is challenging and can be realized by semi-synthesis or total synthesis from appropriate homochiral precursors requiring a complex sequence of protection and deprotection steps in addition to the introduction of the desired functional groups [28][29][30]. A biocatalytic approach aiming to prepare these specific PLs from natural sources is especially preferred when the product's destination is the food or pharmaceutical industry because of the use of harmless, natural and safer reagents [31].…”

Section: Introductionmentioning

confidence: 99%

Valorization of Corn Seed Oil Acid Degumming Waste for Phospholipids Preparation by Phospholipase D-Mediated Processes

Allegretti

¹

,

Bono

²

,

D’Arrigo

³

et al. 2020

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This work focused on the phospholipase D-mediated treatment of the waste residue coming from acid degumming, which constitutes the second part of the degumming step in the crude corn edible oil refining process. This industrial process produces a complex by-product (called gum), a mixture containing phospholipids (PLs) whose composition depends on the nature of the oil source. This residue is usually disposed of with the consequential costs and environmental concerns. An efficient multistep protocol of physical separations of the PL-rich fraction from waste gums has been set up, including centrifugation, precipitation and solvent partitioning. This waste stream, which is thoroughly characterized after the concentration process, constitutes a renewable feedstock for the production of value-added PLs with modified polar head-exploiting phospholipase D-mediated biotransformations, which have been successfully performed on this complex natural mixture. The valorization of these waste gums through the production of high value PLs for targeted applications paves the way to a new alternative approach for their disposal, which could be of great interest from a circular economy perspective.

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A Flexible Synthetic Approach to Phosphatidylglycerols

Cited by 7 publications

References 29 publications

The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol

The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol

The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol

Valorization of Corn Seed Oil Acid Degumming Waste for Phospholipids Preparation by Phospholipase D-Mediated Processes

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