Total Syntheses of Strychnine

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

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 (LD50 = 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. Strychnine ＊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.

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. 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. The First Asymmetric Total Synthesis of (-)-Strychnine Larry E. Overman, J. Am. Chem. SOC.1993, 115, 9293-9294 ＊Strychnine's seven rings displayed ononly 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. Retrosynthetic Analysis:

8. Synthesis:

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

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: