%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