Chapter 38 — Further Reading

Essential textbooks

• Nicolaou, K. C., and Sorensen, E. J. (1996). Classics in Total Synthesis. VCH. The essential reference for studying classic total syntheses. Detailed walkthroughs of Woodward's strychnine, Corey's prostaglandins, Nicolaou's brevetoxin, Eschenmoser-Woodward's vitamin B12, and many more.

• Nicolaou, K. C., and Snyder, S. A. (2003). Classics in Total Synthesis II. VCH. Sequel covering more recent syntheses.

• Nicolaou, K. C., and Sieber, J. D. (2018). Classics in Total Synthesis III. Wiley-VCH. Most recent volume.

• Corey, E. J., and Cheng, X.-M. (1989). The Logic of Chemical Synthesis. Wiley. The book that defined modern retrosynthesis. Chapter 1-3 are foundational reading.

• Warren, S., and Wyatt, P. (2008). Organic Synthesis: The Disconnection Approach, 2nd ed. Wiley. The student-friendly companion to Corey. Worked examples of synthesis design.

• Carreira, E. M., and Kvaerno, L. (2009). Classics in Stereoselective Synthesis. Wiley. Focused on stereocontrol; complementary to Nicolaou's volumes.

Total synthesis history

• Strunz, G. M. (2000). Total Synthesis: A Critical Selection. Wiley.

• Hudlicky, T., and Reed, J. W. (2008). The Way of Synthesis: Evolution of Design and Methods for Natural Products. Wiley-VCH. Connects pure synthesis to industrial process.

• Hudlicky, T., and Reed, J. W. (2011). "Practical synthesis of natural products." Various reviews on industrially-relevant syntheses.

Primary literature: famous total syntheses

• Woodward, R. B., et al. (1956). The morphine synthesis. Journal of the American Chemical Society.

• Woodward, R. B., et al. (1954). The strychnine synthesis. Journal of the American Chemical Society 76, 4749.

• Woodward, R. B., et al. (1956). The cortisone synthesis. Journal of the American Chemical Society 74, 4223.

• Eschenmoser, A., and Woodward, R. B. (1973). The vitamin B12 synthesis. Various papers in Pure and Applied Chemistry and elsewhere.

• Corey, E. J., et al. (1969-onwards). The prostaglandin syntheses. Various papers.

• Corey, E. J., et al. (1988). The ginkgolide B synthesis. Journal of the American Chemical Society 110, 649-651.

• Nicolaou, K. C., et al. (1994). The Taxol synthesis. Nature 367, 630-634.

• Nicolaou, K. C., et al. (1995). The brevetoxin B synthesis. Journal of the American Chemical Society.

• Hayashi, Y., et al. (2009). The oseltamivir synthesis. Angewandte Chemie 48(7), 1304-1307.

• Baran, P. S., et al. (multiple papers). Modern syntheses; many published in Nature and JACS.

Artemisinin specific

• Schmid, G., and Hofheinz, W. (1983). The first total synthesis of artemisinin. Journal of the American Chemical Society 105, 624-625.

• Avery, M. A., et al. (1990). Another total synthesis. Journal of the American Chemical Society 112, 7691-7693.

• Klayman, D. L. (1985). "Qinghaosu (artemisinin): an antimalarial drug from China." Science 228(4703), 1049-1055.

• Tu, Y. (2015). Nobel Lecture. Angewandte Chemie 55(35), 10210-10226.

• Paddon, C. J., et al. (2013). "Sanofi's first commercial-scale production of artemisinic acid in yeast." Nature 496, 528-532.

• Paddon, C. J., and Keasling, J. D. (2014). "Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development." Nature Reviews Microbiology 12(5), 355-367.

Process chemistry and industrial synthesis

• Caron, S., et al. (eds.) (2011). Practical Synthetic Organic Chemistry. Wiley. Industrial perspective.

• Hughes, D. L. (2018). Process chemistry of various drugs. Organic Process Research & Development — many issues. Worth browsing for current practice.

• Magano, J., and Dunetz, J. R. (2011). "Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals." Chemical Reviews 111(3), 2177-2250.

Modern methods reviews

• Hayashi, Y. (2016). "Pot economy and one-pot synthesis." Chemical Science 7, 866-880.

• Caron, S. (2014). "Concepts in process synthesis." Review of green / efficient process design.

• Lerner, R. A., et al. (multiple papers). Catalytic antibodies and biocatalysis.

• Clayden, J., et al. (2018). Various reviews on photoredox catalysis in synthesis.

AI-assisted synthesis

• Coley, C. W., et al. (2017). "Prediction of organic reaction outcomes using machine learning." ACS Central Science 3(5), 434-443.

• Segler, M. H. S., and Waller, M. P. (2017). "Neural-symbolic machine learning for retrosynthesis and reaction prediction." Chemistry — A European Journal 23(25), 5966-5971.

• Coley, C. W., et al. (2023). "A robotic platform for flow synthesis of organic compounds informed by AI planning." Science 380(6644). The 2023 paper showing AI-proposed novel synthesis of natural products.

Computational tools

• Synthia (commercial; Allchemy/Merck): https://www.synthia-online.com/.

• IBM RXN for Chemistry (free): https://rxn.res.ibm.com/.

• AiZynthFinder (open-source from AstraZeneca): https://github.com/MolecularAI/aizynthfinder.

• Avogadro (https://avogadro.cc/): visualize molecules and intermediates.

• PyMOL (https://pymol.org/): visualize protein-ligand complexes for drug design.

Online resources

• Master Organic Chemistry, "Total Synthesis" articles. Free.

• Organic Chemistry Portal (https://www.organic-chemistry.org/). Reaction database with named reactions.

• Nature Chemistry, Science, JACS, Angewandte Chemie: read primary literature for current syntheses.

For practice problems

• Klein, David. Organic Chemistry as a Second Language, 4th ed. Chapter on synthesis design.

• Karty, Joel. Organic Chemistry: Principles and Mechanisms, 2nd ed. (W. W. Norton, 2018).

• Sorrell, Thomas N. Organic Chemistry, 2nd ed. (University Science Books, 2006).

Mathematically inclined readers

• Eschenmoser, A. (1973). On the strategy of B12 synthesis. Various papers.

• Hoffmann, R. (multiple papers). Theoretical synthesis chemistry.

• Houk, K. N. (multiple papers). Computational analyses of organic reactions.

Notes on this chapter's pedagogy

Chapter 38 is the capstone of the textbook. By this point, students have: - Learned the chemistry of every major functional group (Parts I-VII). - Mastered the mechanisms (substitution, addition, acyl substitution, α-carbon, redox, organometallic). - Practiced retrosynthesis (Chapters 14, 31). - Seen the connection to biology (Chapters 32-34). - Understood drug design (Chapter 35).

Chapter 38 brings everything together. The artemisinin case study integrates: - Carbonyl chemistry (Ch 24-28). - α-Carbon chemistry (Ch 27-29). - Diels-Alder + singlet oxygen (Ch 19, 16). - Asymmetric methods (Ch 7, 36, 37). - Synthesis design (Ch 14, 31).

The "art" of synthesis is real, and worth appreciating. After this textbook, the reader is ready to engage with the published literature and continue learning organic chemistry as a discipline that is constantly evolving.

Chapters 39 and 40 cover advanced theoretical topics (pericyclic reactions, Woodward-Hoffmann) and forward-looking themes (green chemistry, AI, the future of synthesis). They cap the book with depth and outlook.