The absolute stereochemistry of phosphoeleganin: A hard challenge in natural products chemistry

The stereochemistry elucidation of acyclic scaffolds is an important challenge in natural products chemistry. Recently, it was isolated a new marine phosphorylated polyketide, phosphoeleganin (1), having a protein tyrosine phosphatase 1B inhibitory activity, from Mediterranean ascidian Sidnyum elegans1. The univocal stereochemical assignment of phosphoeleganin was performed by combination of organic synthesis and chiral derivatization methods directed to the application of UDB concept2-4. According to this method, a complex molecule is composed of structural clusters of stereogenic centers, connected with a number of methylene bridges4. In particular, this method compares the chemical shift of unknown configuration compounds to those of synthetic compounds with known stereochemistry. On this basis, it was considered the C8-C12 stereocluster of phosphoeleganin, in which the S absolute configuration at C8 and the anti-relationship at C11/C12 had been previously assigned1. We decided to compare the 1H and 13C NMR chemical shifts of this stereocluster with those of synthetic compounds with known stereochemistry. Unfortunately, we did not find any suitable model compound for comparison in the Kishi’s universal NMR database; therefore, we decided to prepare the 8,9-anti stereoisomers of tetradecane-5,8,9-triol as models. 1. Imperatore, C.; Luciano, P. Aiello, A.;Vitalone, R.; Irace, C.; Santamaria, R.; Li, J.; Guo,Y.; Menna, M. J. Nat. Prod., 2016, 79, 1144-1148. 2. Kobayashi, Y.; Tezuka, K.; Kishi, Y. Org. Lett., 1999, 1, 2181-2184. 3. Kobayashi, Y.; Tan, C.-H.; Kishi, Y. J. Am. Chem. Soc., 2001, 123, 2076-2078. 4. Higashibayashi, S.; Kishi, Y. Tetrahedron, 2004, 60, 11977-11982.