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1 Total Syntheses of Strychnine Song jin 2012-03-03.

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Presentation on theme: "1 Total Syntheses of Strychnine Song jin 2012-03-03."— Presentation transcript:

1 1 Total Syntheses of Strychnine Song jin 2012-03-03

2 2 Strychnine 士的宁, 番木鳖碱 CAS:57-24-9 * The most common source is from the seeds of the Strtchnos nux vomica tree. * used as a pedticide, particularly for killing small vertebrates such as birds and rodents. A highly toxic (LD 50 = 0.16 mg/kg in rats, 1–2 mg/kg orally in humans) * Strychnine has also served as an inspiration in several books, movies and TV series. (e.g. Count of Monte Cristo ) * First isolated from Strychnos ignati: Pelletier & Caventou, Ann. Chim. Phys. 1818, 8, 323.

3 3 * complex heptacyclic structure (24 skeletal atoms) * 6 contiguous assymetric carbon centers * 5 of those are included within one saturated six-membered ring * 7-membered oxygen heterocyclic motif * "Admittedly, by one whose special familiarity with the intricacies of its structure and behavior might excuse a certain prejudice, but with six nuclear asymmetric centers and seven rings constituted from only twenty-four skeletal atoms, the case is a good one! " ---------(±)-strychnine fist sythesised by R. B. Woodward in 1963, 0.00006% yield, 28 steps. Strychnine

4 4 Syntheses of Strychnine R. B. Woodward - Harvard University (1954) Philip Magnus - University of Texas (1992) Gilbert Stork - Columbia University (1992) Larry E. Overman - University of California, Irvine (1993) Martin E. Kuehne - University of Vermont (1993) Viresh H. Rawal - The Ohio State University (1994) Josep Bonjoch & Joan Bosch - University of Barcelona (1999) Stephen F. Martin - University of Texas (1996-2001) Michael J. Eichberg & K. Peter C. Vollhardt - University of California, Berkeley (2000) Graham J. Bodwell - Memorial University of Newfoundland (2002) Miwako Mori - Hokkaido University (2002) Masakatsu Shibasaki - University of Tokyo (2002) Tohru Fukuyama - University of Tokyo (2004) Albert Padwa - Emory University (2007) Christopher D. Vanderwal. – University of California (2011) David W.C. MacMillian – Princeton University (2011)

5 5 Retrosynthetic Analysis: (1) Larry E. Overman - University of California, Irvine (1993) (2) Christopher D. Vanderwal. – University of California (2011) (3) David W.C. MacMillian – Princeton University (2011)

6 6 The First Asymmetric Total Synthesis of (-)-Strychnine Larry E. Overman, J. Am. Chem. SOC. 1993, 115, 9293-9294 * Strychnine's seven rings displayed on only 24 skeletal atoms still represents a formidable challenge for total synthesis. - Larry E. Overman.(1993) J. Am. Chem. SOC. 1993, 115, 3966 J. Am. Chem. SOC. 1993, 115, 9293 J. Am. Chem. SOC. 1995, 117, 5776

7 7 Retrosynthetic Analysis:

8 8 Synthesis:

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14 14 A synthesis of strychnine by a longest linear sequence of six steps Christopher D. Vanderwal. Chem. Sci., 2011, 2, 649–651 Retrosynthetic Analysis: “strychnine can be considered a benchmark for the state-of-the art in alkaloid synthesis strategy.”

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19 19 Collective synthesis of natural products by means of organocascade catalysis The shortest route to enantioenriched Strychnine David W. C. MacMillan, Nature, 2011, 475, 183 shortest route; 12 steps; 6.4% overall yield. Retrosynthetic Analysis:

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