Notes on CH402 MW component in 20011-2012 academic year:
There will be seven lectures and two workshops associated with the MW part of CH
402. These will be organised as follows:
1) Slides 1-18; Introduction to strategy, disconnections, retrosynthesis, protecting
groups and extreme targets which may include palytoxin, vitamin B12, brevitoxin B,
azadirachtin (4 slides, 6 key steps), vancomycin.
2) Slides 19-28; Early classics of total synthesis in organic chemistry, which may
include colchicine, morphine, strychnine (4 slides, 5 key steps), thienamycin and
penicillin.
3) Slides 29-39; Lessons learnt from the synthesis of small important organic
molecules which may include hirsutene, periplanone B, epothilones (6 slides, 5 key
steps) and prostaglandins.
4) Slides 40-48; Molecules with a high degree of functionality, which may include
avermectin, erythromycin, amphotericin B (6 slides, 4 key steps), Strychnine.
5) Slides 49-56; Construction of highly complex structures which may include
ginkolide B, calicheamycin, taxol (5 slides, 6 key steps).
6) Slides 57-68; The use of cycloadditions in complex molecule synthesis, which may
include FR182877/abyssomicin C (5 slides, 5 key steps), estrone, platensimycin,
progesterone, daphniphylline alkaloids, abyss.
7) Slides 69-80; Enantioselective strategies which may include biotin -arylpropionic
acids, menthol, zaragozic acid, statins (6 slides, 5 key steps).
Each lecture will feature highlights from the synthesis of each target listed, with a
particular focus on the target highlighted in bold and the key steps that are indicated.
The seven targets in bold represent the main material for the workshops and for the
examinable material.
Key references will be provided for each of the seven targets in bold, and these papers
should be treated as examinable material however you do not have to learn the content
by heart but should ensure that you understand the reasons for the choice of strategy
and the main mechanisms.
The references are as follows and are downloadable either directly from the journal or
through links from the Prof M. Wills website. Warwick has a subscription to each of
the journals cited. Note that the references may be provided for teaching purposes
only, and only within this course. For each target there is either one recent review or
three-four short papers.
1) Azadirachtin: ‘The Azadirachtin Story, by G. E. Veitch, A. Boyer and S. V. Ley,
Angew. Chem. Int. Ed. 2008, 47, 9402-9429.
2) Strychnine. a) A synthesis of strychnine by a longest linear sequence of six steps’
D. B. C. Martin and C. D. Vanderwal, Chemical Science, 2011, 2, 649-651. b) S. D.
Knight, L. E. Overman and G. Pairaudeau, J. Am. Chem. Soc. 1993, 115, 9293–9294.
c) T. Ohshira, Y. Xu, R. Takita, S. Shimizu, D. Zhong and M. Shibasaki, J. Am.
Chem. Soc, 2002, 124, 14546-14547. d) G. Sirasani, T. Paul, W. Dougherty Jr., S.
Kassel and R. B Andrade, J. Org. Chem. 2010, 75, 3529-3532.
3) Epothilones; ‘Epothilones – a fascinating family of microtubule stabilizing
antitumor agents’, J. Mulzer, K.-H. Altmann, G. Höfle, R. Müller and K. Prantz, C. R.
Chemie 2008, 11, 1336.
4) Amphotericin B. a) Synthesis of 35-deoxy amphotericin B methyl ester: a strategy
for molecular editing;, A. M. Szpilman, D. M. Cereghette, N. R. Wurtz, J. M.
Manthorpe and E. M. Carreira, Angew. Chem. Int. Ed. 2008, 47, 4335-4338. b) Total
synthesis of (+)-roxacitin via C-C bond forming transfer hydrogenation...’ S. B. Han,
A. Hassan, I. S. Kim and M. J. Krische, J. Am. Chem. Soc. 2010, 132, 15559-15561.
c) K. C. Nicolaou, R. A. Daines, J. Uenishi, W. S. Li, D. P. Paphatjis and T. K.
Chakraborty, J. Am. Chem. Soc. 1988, 110, 4672-4685.
.
5) Taxol; a) ‘The Conquest of Taxol’, K. C. Nicolaou and R. K. Guy, Angew. Chem.
Int. Ed. 1995, 34, 2079-2090. b) R. A. Holton, H.-B. Kim, C. Somoza, F. Liang, R. J.
Biediger, P.D. Boatman, M. Shindo, C. C. Smith, S. Kim, H. Nadizadeh, Y. Suzuki,
C. Tao, P. Vu, S. Tang, P. Zhang, K. K. Murthi, L. N. Gentle and J. W. Liu, J. Am.
Chem. Soc. 1994, 116, 1599-1600. c) P. Bremond, G. Audran and H. Monti, J. Org.
Chem. 2008, 73, 6033-6036.
6) FR182877. a) D. A. Vosberg, C. D. Vandewall and E. J. Sorensen, . J. Am. Chem.
Soc. 2002, 124, 4552-4553. b) D. A. Evans and J. T. Starr, Angew. Chem. Int. Ed..
2002, 41,1787-1790. c) C. W. Zapf, B. A. Harrison, C. Drahl and S. J. Sorenson,
Angew. Chem. Int. Ed.. 2005, 44,6533-6537. d) K. C. Nicolaou and S. T. Harrison. J.
Am. Chem. Soc. 2007, 129, 429-440.
7) Statins. a) M. Hirama and M. Uei, J. Am. Chem. Soc. 1982, 104, 4251-4253. b) T.
Sammakia, D. J. Johns, G. Kim and M. A. Berliner, J. Am. Chem. Soc. 2005, 127,
6504-6505. c) J. Robichaud and F. Tremblay, Org. Lett. 2006, 8, 597-600.
Exam structure.
The exam will test your understanding of the synthetic strategies towards the seven
targets in each section of the course, why they were selected and why particular routes
were chosen. You will be told which steps to focus revision on.