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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010The Total Regioselective Control of Tartaric AcidJan Spengler 1,2 , Ana I. Fernández-Llamazares 1,2 ,Javier Ruiz-Rodríguez 1,2 , Klaus Burger 3 , and Fernando Albericio 1,2,41 Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028,Barcelona, Spain; 2 CIBER-BBN, Networking Centre on Bioengineering, Biomaterials andNanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain;3 Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103, Leipzig,Germany; 4 Department of Organic Chemistry, University of Barcelona, Martí i Franqués1-11, 08028, Barcelona, SpainIntroductionTartaric acid is a structurally simple molecule which has found many applications inorganic chemistry as a chiral pool compound. In peptide chemistry, it is a starting materialfor the total synthesis of natural and non-natural amino acid or hydroxy acids, and it servesas scaffold or core for (depsi) peptides [1].The use of tartaric acid as a chiral building block often requires the appropriatedifferentiation between the functional groups present in its structure. The distinctionbetween the two pairs of hydroxy and carboxy groups are easy to accomplish. Thesefunctionalities can be efficiently mono-derivatized by several methods. However, what stillremains a challenge is the independent modification of the carboxy and the hydroxy groupin a regioselective manner, which is crucial for the synthesis of certain products. Thestrategies reported to date require extensive preparative work, considerable study ofreaction conditions, structural assignments, and sometimes cumbersome or impossibleseparations between regioisomers.Results and DiscussionHerein we disclose an efficient strategy to synthesize tartaric acid derivatives bearingorthogonal sets of hydroxy and carboxy protecting groups. These 1-carboxy-2-hydroxy,and 1-carboxy-3-hydroxy protected building blocks can be prepared on a multi-gram scale(4-8 steps starting from L-tartaric acidor L-dimethyl tartrate, respectively,with overall yields between 38 – 56%).Differentiation of all functionalgroups is achieved by the reaction ofO-monobenzylated tartaric acid [2]with hexafluoroacetone (Figure 1). Thisreaction takes place with absoluteselectivity exclusively affording thefive-membered heterocycle. This dioxolanoneis a key intermediatebecause each of the two carboxylgroups can be selectively derivatized,depending on the synthetic transformationsthat are carried out. In thisFig. 1. PG 1 : Bzl, p-nitrobenzyl, p-methoxybenzyl; PG 2 : Me, allyl, tert-butyl. way, all the four functional groups oftartaric acid can be modified withoutproducing regioisomers [3].These tartaric acid derivatives may contribute to significantly speed up the synthesesof products in which all four functional groups of tartaric acid have to be differentiated.Moreover, the use of these building blocks in some established synthetic routes should nowmake it possible to obtain products with additional points for structural modification.130