%0 Journal Article %A Gutiérrez, Marcelino %A Andrianasolo, Eric H. %A Shin, Won Kyo %A Goeger, Douglas E. %A Yokochi, Alexandre %A Schemies, Jörg %A Jung, Manfred %A France, Dennis %A Cornell-Kennon, Susan %A Lee, Eun %A Gerwick, William H. %D 2009 %T Structural and Synthetic Investigations of Tanikolide Dimer, a SIRT2 Selective Inhibitor, and Tanikolide seco-Acid from the Madagascar Marine Cyanobacterium Lyngbya majuscula %U https://acs.figshare.com/articles/journal_contribution/Structural_and_Synthetic_Investigations_of_Tanikolide_Dimer_a_SIRT2_Selective_Inhibitor_and_Tanikolide_i_seco_i_Acid_from_the_Madagascar_Marine_Cyanobacterium_i_Lyngbya_majuscula_i_/2837041 %R 10.1021/jo900578j.s002 %2 https://acs.figshare.com/ndownloader/files/4534747 %K Madagascar marine cyanobacterium Lyngbya majuscula %K tanikolide %K SIRT 2 %K GC %K compound %K conjunction %K chiral HPLC analyses %K dimer %K Tanikolide %K SIRT 2 inhibitor %K synthesis %K 2.4 μ M %K NMR %K MS %K IC %X Tanikolide seco-acid 2 and tanikolide dimer 3, the latter a novel and selective SIRT2 inhibitor, were isolated from the Madagascar marine cyanobacterium Lyngbya majuscula. The structure of 2, isolated as the pure R enantiomer, was elucidated by X-ray experiment in conjunction with NMR and optical rotation data, whereas the depside molecular structure of 3 was initially thought to be a meso compound as established by NMR, MS, and chiral HPLC analyses. Subsequent total synthesis of the three tanikolide dimer stereoisomers 4, 5, and ent-5, followed by chiral GC−MS comparisons with the natural product, showed it to be exclusively the R,R-isomer 5. Tanikolide dimer 3 (= 5) inhibited SIRT2 with an IC50 = 176 nM in one assay format and 2.4 μM in another. Stereochemical determination of symmetrical dimers such as compound 3 pose intriguing and subtle questions in structure elucidation and, as shown in the current work, are perhaps best answered in conjunction with total synthesis. %I ACS Publications