Orded the deprotected diols 9 and 10 in higher purity and in good yields (78?1 ). We used a two-prong strategy to the regioselective manipulation on the sn-2 and sn-3 hydroxyl groups of compounds 9 and ten for preparation with the functionalized / substituted sn-3-carbinols (Scheme 1). A single system relied on a sequence of reactions that integrated 1) tritylation of the main hydroxyl group, two) acylation on the secondary alcohol function to introduce the sn-2-ester group, and 3) acid catalyzed cleavage from the trityl group to obtain the preferred sn-3-alcohol for the subsequent phosphorylation step. Along these lines, reaction in the dodecyl ester of glyceric acid 9 with triphenylmethyl chloride, inside the presence of collidine, in dichloromethane yielded the corresponding trityl ether 11 (80 ), which was subsequently acylated with coumarin-labeled decanoic acid making use of DCC / DMAP (72 ), and lastly detritylated to produce the sn-3-carbinol 13 (61 ). Inside a related series of reactionsTetrahedron. Author manuscript; available in PMC 2015 May perhaps 13.Rosseto and HajduPagedodecylamide of glyceric acid 10 was initially converted to 15 by tritylation on the principal hydroxyl group (72 ), followed by acylation in the sn-2-position (95 ) and detritylation to obtain the substituted glycerol 17 in 79 yield.3-Bromo-5-methylbenzonitrile Order This three-step sequence readily created the preferred glyceric acid derivatives because the precursors required for phosphorylation, however, application on the technique expected improvement of rigorous experimental circumstances, precise for every substrate, inside the last step of your sequence, inside the course with the detritylation reaction. Especially, since it has recently been well demonstrated, the experimental circumstances needed to stop acid-catalyzed acyl migration to a neighboring hydroxyl group is extremely significantly dependent on the structure with the acyl group involved.(R)-2-Chloro-2-fluoroacetic acid Formula 15 Along these lines it has been shown that even minor structural variations (such as the chain-length with the acyl group) make a important difference in terms of the distinct experimental conditions that need to be employed to stop acyl migration.PMID:26446225 15b Consequently, so that you can create a more robust process for regioselective manipulation of your diol portion from the molecule, we turned to an option approach relying on orthogonal protection at the sn-2- and sn-3-positions. To that impact, we employed the base-labile phenoxyacetyl group for protection with the primary alcohol function,16 as well as the acid-labile tetrahydropyranyl function to protect the secondary hydroxyl group. First the phenoxyacetyl group was introduced in reaction of compounds 9 and ten with phenoxyacetyl chloride in chloroform at 0?C, utilizing two,four,6-collidine as catalyst.16 The sn-3-phenoxyacetyl compounds 12 and 16 were obtained in 68 yield.17 The regioselectivity with the reaction could readily be confirmed by the observation that both sn-3-phenoxyacetyl esters showed base-line 1HNMR absorption inside the five.00?.ten range, that is constant with the presence in the no cost sn-2-hydroxyl group inside the goods.15 In the next step, tetrahydropyranylation on the hydroxyl group in the sn-2-position was carried out making use of excess of three,4-dihydro-2H-pyran with PPTS as catalyst in dichloromethane. Subsequent chemoselective base-hydrolysis in the phenoxyacetyl ester with tert. butylamine in a mixture of methanol-chloroform afforded the sn-3-carbinols 14 and 18 in 91?7 all round yields. Despite the fact that introduction of the tetrahydropyranyl group developed a second chiral center within the mo.
