title: Synthesis of functionalized 1,3-thiazine libraries combining solid-phase synthesis and post-cleavage modification methods.
abstract: The solid-phase synthesis of diverse sets of 1,3-thiazine-5-carboxylates on Wang resin is described. Acetoacetylation, followed by Knoevenagel condensation and an acid-promoted ring-closure reaction with thioureas furnished polymer-bound 1,3-thiazines. As an alternative to transesterification, a de-novo synthesis of beta-keto esters, starting from polymer-bound malonic acid through reaction with acyl imidazoles, was applied to increase the diversity. To reduce contamination, an on-bead purification of resin-bound 1,3-thiazines that makes use of differences in the reactivity of ester bonds toward alkoxides is reported. A final four-step post-cleavage modification of thiazine-5-carboxylates, derived by TFA cleavage from the Wang linker, leads to esters or amides. Twenty 1,3-thiazines were obtained in yields of up to 61 % over either 9 or 13 steps.
authors.affiliation: Institute of Chemistry, Organic and Bioorganic Chemistry, Karl-Franzens University Graz, Heinrichstrasse 28, 8010 Graz, Austria.
authors.forename: Gernot A
authors.initials: GA
authors.lastname: Strohmeier
authors.forename: Willibald
authors.initials: W
authors.lastname: Haas
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Kappe