Chemical library in place Robust HT screen Hit Identification Chemical and biological validation Used to study biological processes Potential therapeutic A focus on the NF-  B signaling cascade chemical tool Identify inhibitors of NF-  B activation arthritis, sceptic shock, inflammatory bowel disease Inhibitors already known... In collaboration with Prof. Ron Hay FRS Life Sciences Dundee Bremner and Heinrich, 2002, J. Pharmacy and Pharmacol., 54,

Chemical library in place Robust HT screen Hit Identification Chemical and biological validation Used to study biological processes Potential therapeutic Luciferase based Reporter gene assay Raquel Frade, Ron Hay Nick Westwood A focus on the NF-  B signaling cascade Natural Product collection from Professor Alan Harvey, SIDR University of Strathclyde Luc NF-  B Identify inhibitors of NF-  B activation

Chemical library in place Robust HT screen Hit Identification Chemical and biological validation Used to study biological processes Potential therapeutic Luciferase based reporter gene assay Raquel Frade, Prof Ron Hay FRS Nick Westwood A focus on the NF-  B signaling cascade Natural Product collection from Professor Alan Harvey, SIDR University of Strathclyde extract purification Raquel Frade Tanacetum parthenium Identify inhibitors of NF-  B activation structure assignment Dr Tomas Lebl

solvent A sesquiterpene lactone?

(1H)(1H)  ( 13 C) (4.65)-71.8 (72.0) MS : 279 [M + H] + Assignment of the structure of the major component in the purified bioactive extract Tomas Lebl

Structurally related compounds R =  -OAc (S), R 1 = H R =  -OAc (R), R 1 = H R =  -OMe (S), R 1 = H R =  -OMe (R), R 1 = H R =  -OH (S), R 1 = OH R =  -OH (S), R 1 = OH R =  -OAc (S), R 1 = OH R =  -OAc(S), R 1 = OH R =  -OH (S), R 1 = H iso-secotanapartholide From Artemisia rutifolia no report of  -OH isomer Zdero, Bohlmann et al., 1986, Phytochem., 25, ; Jia et al., 1991, Phytochem., 30, ; Oksuz, 1990, Phytochem., 29, ; Toth et al., 2003, Tet., 59,

Structurally related compounds R =  -OAc (S), R 1 = H R =  -OAc (R), R 1 = H R =  -OMe (S), R 1 = H R =  -OMe (R), R 1 = H R =  -OH (S), R 1 = OH R =  -OH (S), R 1 = OH R =  -OAc (S), R 1 = OH R =  -OAc(S), R 1 = OH R =  -OH (S), R 1 = H iso-secotanapartholide secotanapartholides Knight et al., 1996, J.Chem.Soc., Perkin Trans. 1, and references therein.

Chemical library in place Robust HT screen Hit Identification Chemical and biological validation Used to study biological processes Potential therapeutic Edward Makiyi, Susan Cobb Synthesis of authentic material to clarify stereochemistry issues at C3 A focus on the NF-  B signaling cascade Identify inhibitors of NF-  B activation

Proposed biosynthesis of the secotanapartholides Bohlmann and Zdero, 1982, Phytochem., 21, ; Knight et al., 1996, J.Chem.Soc., Perkin Trans. 1, ; Rucker et al., 1992, Planta Med., 58, 293. and  -isomer

Proposed biosynthesis of secotanapartholide Bohlmann and Zdero, 1982, Phytochem., 21, ; Knight et al., 1996, J.Chem.Soc., Perkin Trans. 1, ; Rucker et al., 1992, Planta Med., 58, 293.

A biomimetic approach to iso-secotanapartholides? Geissman and Winters, 1968, Tet. Lett., 27, Artabsin

A biomimetic approach to iso-secotanapartholides? (1H)(1H) , , , , , , , , OMe 3.41 Ji et al., 1991, Phytochem., 30,

An alternative semi-synthesis approach late stage oxidative cleavage with no protecting groups

Synthesis of diastereomeric diols Buchi et al., 1966,J. Am. Chem. Soc., 88, Prof. Alex Slawin

... and then diastereomeric triols Prof. Alex Slawin

... and then diastereomeric triols

Synthesis of 3  -OH-iso-secotanapartholide Greico et al., 1974, J.Org.Chem., 39,

Synthesis of epi-3  -iso-secotanapartholide.. and then for the comparison with the natural material Thanks to Professors Todorova, Marco, Lee, Ryu and Saliba Does anyone have any seco-tanapartholide?

A comparison of iso-secotanapartholides with our isolated natural material Natural source  -OH synthetic epi  -OH 500MHz, CD 3 CN

Identify key biological process Chemical library in place Robust HT screen Hit Identification Chemical and biological validation Used to study biological processes Potential therapeutic A focus on the NF-  B signaling cascade Luc NF-  B and 3  -isomer