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

Abstract

We propose O-silylated C3-halohydrins [1(3)-O-silyl-2-O-acyl-, 1,2(2,3)-O-bis(silyl)-, and 1(3)-O-acyl-2-O-silyl-3(1)-halo-sn-glycerides] as new chirons in the total synthesis of glycerolipid constructs. These are efficiently producible via opening of the oxirane ring of the corresponding glycidyl derivatives and permit (i) displacement of the iodine by a requisite carboxylate in the presence of O-triisopropylsilyl (O-TIPS), O-tert-butyldimethylsilyl (O-TBDMS), and O-acyl substituents; (ii) selective acylation across an appropriate silyloxy system [e.g., O-TBDMS or O-triethylsilyl (O-TES)] of monoesterified haloglycerides; (iii) direct exchange of an O-silyl protection (e.g., O-TBDMS or O-TIPS) for a trichloroacetyl group; (iv) conversion of a terminal TBDMS group into the corresponding trifluoroacetate without affecting O-TIPS-, O-acyl- and iodo functions. The above transformations secure flexible routes to a variety of otherwise difficult-to-access key-intermediates [e.g., 1,2(2,3)-O-bis(acyl)-3(1)-trichloroacetyl-, 1,3-O-bis(acyl)-2-trichloroacetyl-, 1,2(2,3)-O-bis(acyl)-3(1)-O-TBDMS/TIPS-, 1,3-O-bis(acyl)-2-O-TIPS/TBDMS-, 1(3)-O-acyl-2-O-TIPS-, 1,2(2,3)-O-bis(acyl)-3(1)-iodo-sn-glycerols, etc.] and lend themselves to a powerful methodology for the preparation of di- and triacylglycerols as well as glycerol-based cationic lipids. The reactions involved are entirely regio- and stereospecific, avoid acyl migration, and can provide target compounds with a chosen absolute configuration from a single synthetic precursor.

Bifunctional probes reveal the rules of intracellular ether lipid transport

“…Similar transformations have been reported previously [39][40][41] , but the utilized reagents gave unsatisfactory yields in our hands, presumably due to the longer chain length and the presence of the diazirine and alkyne groups.…”

“…Many different reagents, both bases and Lewis-acid catalysts, have been described in the literature to afford high yields in similar transformations. [40,41,[44][45][46][47][48][49][50][51][52] In our hands, the epoxide opening worked best with catalytic amounts of Sc(OTf)3 (5 mol%) in dry DCM, [52] whereas most published protocols gave either very low yields or no product at all (see SI for details). The bifunctional 1-alkyl-glycerol ether 15 was isolated in 59% yield under optimized reaction conditions (3.5 equivalents of epoxide 14 added, longer reaction time and addition of a second batch of catalyst after 24 h).…”

Green synthesis of glycerol 1,3-bromo- and iodohydrins under solvent-free conditions

“…In contrast to the glycerol chloro-and bromohydrins, the glycerol iodohydrins have been applied in various pharmaceutical preparations because for their antiseptic, mucolytic and fungicide properties (34,35). Some glycerol iodohydrins were used in the synthesis of cardiolipins (36,37), as key intermediates of a promising class of drugs in treating type 2 diabetes (19,38), and applied in organic synthesis as a building block to produce other chemicals (39,40).…”

Identification of triacylglycerols in coix seed extract by preparative thin layer chromatography and liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry

“…5,6 This results in the different bioavailability of FAs depending on their sn-position. 7,8 Thus, identification of TAGs and DAGs in coix seed is required for nutritional and pharmaceutical understanding of coix seed widely used as food and medicine. There are, however, a few reports on determination and identification of TAGs and DAGs in coix seed.…”