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

Abstract

Trichloroacetylation of 1-acyl-3-O-tert-butyldimethylsilyl-sn-glycerols, followed by a direct conversion of the silyl protecting group into an ester functionality by means of a reagent system: tetra-n-butylammonium bromide (TBABr)-trimethylsilyl bromide (TMSBr)-carboxylic acid anhydride (CAA), constitutes an efficient protocol for the preparation of enantiomerically pure 1,3-diacyl-sn-glycerols in high yields.

Regioselective and Stereospecific Halosilylating Cleavage of the Oxirane System of Glycidol Derivatives as an Efficient Strategy to C2‐O‐Functionalized C3‐Vicinal Halohydrins

“…As shown in entry 3, TFAA in the presence of TMSX (X = Cl, Br, or I), was also inefficient in replacing the trimethylsilyl group in the model substrate by a trifluoroacetyl one, although it is known that this system generates highly electrophilic species, trifluoroacetyl halides. [54] The latter reactions, however, could be rescued by the addition of the corresponding Bu 4 NX (entry 4).…”

“…[54] Although utility of this reagent can be extended to the production of vicinal bromoesters, it appeared to be less suitable for the synthesis of C2-O-acylated C3-vicinal chloro-and iodohydrins from the corresponding O-trimethylsilyl congeners (e.g., type 4 and 8, Scheme 6) as a result of the competitive formation of bromohydrin byproducts (ca. 10-20 %, 1 H and 13 C NMR spectroscopy).…”

“…[48,49] Examples of a direct conversion of various silyloxy systems (e.g., trimethylsilyl-, tert-butyldimethylsilyl-, triisopropylsilyl-, tert-butyldiphenylsilyl ethers, etc.) into either acetates (e.g., by using FeCl 3 -acetic anhydride, [50] pyridineacetic anhydride-acetic acid, methanol-acetic acid, [51] ZnCl 2 -acetyl chloride, [52] or SnBr 2 -acetyl bromide [53] ) or higher carboxylates [54] are known from the literature. These methods, however, (i) involve chemical procedures that are incompatible with trifluoroacetyl derivatives, (ii) are not selective towards any of the commonly employed silyl transient protections, and (iii) are inapplicable to the synthesis of C3-vicinal haloalkanols bearing a terminal acyl group.…”

Direct Trifluoroacetylation Across a Trimethylsilyloxy System as a Stereo­specific, Chemo- and Regioselective Approach to C3-Vicinal Halohydrins

“…As shown in entry 3, TFAA in the presence of TMSX (X = Cl, Br or I) was also inefficient in replacing the trimethylsilyl group in the model substrate by trifluoroacetyl, although it is known that this system generates highly electrophilic species, trifluoroacetyl halides. 25 The latter reactions, however, could be rescued by the addition of the corresponding Bu 4 NX (entry 4).…”

Regioselective, Haloacylating Cleavage of an Oxirane System Mediated by Trifluoroacetic Anhydride/Trimethylsilyl Halides: An Efficient Entry to 2-Acyl-3-haloglycerols

“…Since we previously found that treatment of carboxylic acid anhydrides with TMSX (e.g. X = Br or I, 1.0 equiv) at room temperature led to almost instantaneous formation of equimolar amounts of the corresponding acyl halides (ACX) and trimethylsilyl carboxylates (ACOTMS), 34 we carried out additional experiments to elucidate mechanistic contribution of these species in the haloacylating cleavage of the aforementioned oxirane systems. 1 H NMR and 13 C NMR spectroscopy revealed that acetyl bromide (1.5 equiv) alone effected opening of the oxirane ring of glycidyl oleate 1 with a predominant migration of the oleoyl moiety affording a mixture of 1-acetyl-2oleoyl-and 1-oleoyl-2-acetyl-3-bromoglycerol in a ratio of 80:20 (CH 2 Cl 2 , r.t., 72 h, isolated yield as a mixture: ca.…”