Regioselective and stereospecific acylation across oxirane- and silyloxy systems as a novel strategy to the synthesis of enantiomerically pure mono-, di- and triglycerides

Abstract

A trifluoroacetate-catalyzed opening of the oxirane ring of glycidyl derivatives bearing allylic acyl or alkyl functionalities with trifluoroacetic anhydride (TFAA), provides an efficient entry to configurationally homogeneous 1(3)-acyl- or 1(3)-O-alkyl-sn-glycerols. Selective introduction of tert-butyldimethylsilyl- (TBDMS), or triisopropylsilyl- (TIPS) transient protections at the terminal sites within these key intermediates secures 1(3)-acyl- or 1(3)-O-alkyl-3(1)-O-TBDMS (or TIPS)-sn-glycerols as general bifunctional precursors to 1,2(2,3)-diacyl-, 1(3)-O-alkyl-2-acyl- and 1,3-diacyl-sn-glycerols and hence triester isosters. Incorporation of a requisite acyl residue at the central carbon of the silylated synthons with a subsequent Et(3)N.3HF-promoted, direct trichloroacetylation across the siloxy system by trichloroacetic anhydride (TCAA), followed by cleavage of the trichloroacetyl group, affords the respective 1,2(2,3)-diacyl- or 1(3)-O-alkyl-2-acyl-sn-glycerols. Alternatively, a reaction sequence involving: (i) attachment of a trichloroacetyl fragment at the stereogenic C2-centre of the monosilylated glycerides; (ii) replacement of the silyl moiety by a short- or long-chain carboxylic acid residue by means of the acylating agent: tetra-n-butylammonium bromide (TBABr)-carboxylic acid anhydride (CAA)-trimethylsilyl bromide (TMSBr); and (iii) removal of the trichloroacetyl replacement, provides pure 1,3-diacyl-sn-glycerols. The TBABr-CAA-TMSBr reagent system allows also a one-step conversion of 1,2-diacylglycerol silyl ethers into homochiral triglycerides with predefined asymmetry and degree of unsaturation. These compounds can also be accessed via a two-step one-pot approach where the trichloroacetyl derivatives of 1,2(2,3)- or 1,3-diacyl-sn-glycerols serve as triester building blocks for establishing the third ester bond at preselected C3(1)- or C2-positions within the glycerol skeleton at the very last synthetic stage. In all instances, the target compounds were produced under mild conditions, in high enantiomeric purity, and in practically quantitative yields.

Regioisomeric and enantiomeric analysis of triacylglycerols

“…In conclusion, we believe that the potential of SFC or the newly developed UPC 2 has not yet been exhausted. To our current knowledge, enantiomers of TAG have not yet been separated.…”

“…However, the "optical activity" of these TAG is usually too low to be measured. For example, sn-1-oleoyl-2,3-dipalmitoyl-sn-glycerol (sn-O/P/P) has [a] D 20 ¼ 0.00 (c 7.05, CHCl 3 ) [2].…”

Separation and Identification of Odd Chain Triacylglycerols of the Protozoan Khawkinea quartana and the Mold Mortierella alpina Using LC–MS

“…The same applies to the optical properties such as optical rotation or ORD (optical rotatory dispersion), as their values approach zero. For instance, for 1-oleoyl-2,3-dipalmitoyl-sn-glycerol the [a] D 20 = 0.00 (c 7.05, CHCl 3 ) [32].…”

A novel method for the synthesis of symmetrical triacylglycerols by enzymatic transesterification

“…In the past five decades, only chemical (Stamatov and Stawinski, 2007;Vaique et al, 2010;Awl et al, 1989) and chemoenzymatic methods (Andrews et al, 2008;Haraldsson et al, 2000;Magnusson and Haraldsson, 2010) were reported for the synthesis of high regiopurity symmetrical TAGs with PUFAs at the sn-2 position in the literature. In these methods, many toxic solvents and reagents, such as 4-dimethylaminopyridine (DMAP), N-ethyl-N 0 -( 3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCI) and fatty acid chloride were used.…”