Synthesis of long-chain 1-saturated-2-unsaturated diacylglycerols via levulinoyl protection

Levulinic acid in organic synthesis

“…54 However, hydrazinolysis is the most efficient method for deprotection. 55,56 Under mild conditions, LA esters quantitatively react with hydrazine and its derivatives, which results in the regeneration of the original alcohol and the formation of the corresponding dihydropyridazinone, as a result of which the acid is completely eliminated from subsequent reaction. The formation of dihydropyridazinones and their reactivities are discussed in Section V.…”

O-Silylated C3-halohydrins as a novel class of protected building blocks for total, regio- and stereocontrolled synthesis of glycerolipid frameworks

“…Total synthesis of 1,2(2,3)-O-diacyl-sn-glycerols and derivatives thereof usually makes use of naturally occurring chiral species [e.g., D-mannitol, 7 D-or L-serine, 55 L-glyceric acid, 56 L-erythrulose, 57 or sn-glycero-3-phosphocholine 41 ] or synthetic building blocks (e.g., glycerol acetals, 15,45,58 various glycidol derivatives, 47, 59 and others 5,18 ) that can be elaborated by chemical 5, 16 or chemoenzymatic 18,60 techniques to an enantiomerically pure 1(3)-monoacyl-sn-glycerol [1(3)-MAG] bearing a transient protection at the other primary hydroxyl function.…”

“…55 Although advocated as superior to protectiondeprotection protocols, this method and its latter modifications 67 suffer from lack of generality and harsh reaction conditions that contribute to formation of transesterification products, acyl migration, epimerization, oxidation, etc. 59 One-step methodologies based on esterification of 1-monoglycerides with various acyl donors, seem to be equally inefficient 16 and afford 1,3-diglycerides in low yields (44-46%). 25,42 These difficulties prompted us to consider 1-O-tertbutyldimethylsilyl-2-O-triisopropylsilyl-3-iodo-sn-glycerol (13) as a new building block (halohydrin of type II) in the synthesis of 1,3-DAGs (Scheme 4), to permit a direct incorporation of an acyl group into any position of the glycerol skeleton.…”

Direct Acylation across a Silyloxy System of Glycerol with Carboxylic Acid Anhydrides: A Novel Strategy to the Prodrug Carrier Modules - 1,3-Diacyl-sn-glycerols

“…lack of generality, mediocre yields (40-70% 17 ), separation problems, 18 and rather harsh reaction conditions that contribute to formation of transesterification products, acyl migration, racemization, oxidation, etc. [15][16][17]19 Alternative synthetic protocols based on esterification of 1-monoglycerides with various acyl donors, seem to be equally inefficient due to analogous drawbacks 20 and usually afford unsymmetrical 1,3-diglycerides in low yields (44-46% 5,21 ). It is also noteworthy that all the above methodologies require painstaking chromatographic separation, 5,10,[15][16][17]21,22 and the purification process by itself frequently triggers intramolecular ligands migration.…”