Lecule, it did not complicate the isolation and purification with the items.18 It need to be pointed out that a single substantial benefit on the phenoxyacetyl / tetrahydropyranyl tactic is that it completely circumvents the issue of acyl migration in the sequence. The second phase of your synthesis, shown in Scheme two, focused on elaboration with the sn-3phosphocholine headgroup on the target compounds. To attain efficient phosphorylation of your substituted glyceric acid derivatives we utilized 2-chloro-2-oxo-1,3,2-dioxaphospholane, as this reagent has been shown to create phosphocholine derivatives in fantastic yields and with handful of byproducts, even in reactions with substrates that carry nucleophilic amide-carbonyl groups that are extensively regarded as rather hard substrates to phosphorylate.19 Thus, reaction between ethylene chlorophosphate and also the substituted glyceric acid series of 13 and/or 17 in benzene, inside the presence of triethylamine as catalyst, followed by nucleophilicNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTetrahedron. Author manuscript; readily available in PMC 2015 May possibly 13.Rosseto and HajduPagering-opening of your cyclic phosphodiester intermediates with trimethylamine in anhydrous acetonitrile made the corresponding phosphocholine compounds (Scheme 2).NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThe phospholipid goods 19 and 20 were purified by silica gel chromatography, and isolated in 48?4 overall yields.20 Similarly, phosphorylation with the sn-2tetrahydropyranyl protected glyceric acid derivatives 14 and 18 afforded the corresponding phosphorylcholines 21 and 23 in somewhat higher all round yields (67?four ). The third and final phase of your synthesis focused on building a approach to replace the sn-2-tetrahydropyranyl guarding group in compounds 21 and 23 with all the series of sn-2ester groups from the target phospholipids.Formula of 1450879-67-0 The sequence shown in Scheme 2 proceeded by way of formation of lysophospholipid intermediates 22 and 24 that had been prepared by acid-catalyzed cleavage on the sn-2-tetrahydropyranyl group of the phosphorylated compounds. Therefore, phospholipid 21 treated with dilute hydrochloric acid in aqueous dioxane yielded lysophospholipid 22 (94 ), and deprotection of 23 was accomplished utilizing a biphasic system comprised of aq.5-Bromo-2-chlorothiazolo[5,4-b]pyridine Chemscene HCl and chloroform that made the corresponding lysophospholipid 24 isolated by silica gel chromatography in 57 yield.PMID:25147652 With compounds 22 and 24 in hand, we proceeded to introduce a series of sn-2-fatty acyl groups for preparation of mixed-chain double labeled phospholipid compounds, such as these that would carry chain-terminal reporter groups. We’ve utilised two approaches for introduction of your sn-2-substituents: 1) acylation with the lysophospholipid analogues with fatty acyl groups already labeled at their chain-end, and two) incorporating fatty acyl groups having a chain-terminal protecting group, to elaborate the reporter group just after the acylation step. As a result, reaction amongst lysophospholipid 22 and 7-mercapto-4-methylcoumarin labeled decanoic acid, utilizing DCC / DMAP in chloroform, with added glass-beads and sonication to enhance the glass surface within the reaction vessel,21 yielded the phospholipid product 20 (62 ), with an sn-2-acyl group carrying the chain-terminal fluorophore. In an alternative sequence, lysophospholipid 24 was initial acylated in reaction with FMOCprotected 12-aminododecanoic acid working with DCC / DMAP in chloroform, creating phospholipid.
