A Longitudinal Study of Alkaloid Synthesis Reveals Functional Group Interconversions as Bad Actors Steven W. M. Crossley and Ryan A. Shenvi* Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States CONTENTS 1. Introduction B 2. General Strategies: Historical Threads C 2.1. General Strategies. Reduction (Scheme 2) C 2.2. General Strategies. Mannich Reactions/Cas- cades (Scheme 3) E 2.3. General Strategies. Radical Amination of C-H Bonds (Scheme 4) G 2.4. General Strategies. Pericyclic Reactions (Scheme 5) H 2.5. General Strategies. Hydroamination (Scheme 6) I 2.6. General Strategies. Rearrangements (Scheme 7) J 3. Syntheses K 3.1. Loline K 3.1.1. Tufariello’s Synthesis of (±)-Loline (1986) (Scheme 8) K 3.1.2. White’s Synthesis of (+)-Loline (2000/ 2001) (Scheme 9) L 3.1.3. Scheerer’s Synthesis of (±)-Acetylnorlo- line (2011) (Scheme 10) M 3.1.4. Trauner’s Synthesis of (+)-Loline (2011) (Scheme 11) N 3.1.5. Loline Conclusion N 3.2. Gephyrotoxin 287C O 3.2.1. Kishi’s Synthesis of (±)-Gephyrotoxin 287C (1980) (Scheme 12) O 3.2.2. Hart’s Synthesis of (±)-Gephyrotoxin 287C (1981/1983) (Scheme 13) P 3.2.3. Overman’s Synthesis of (±)-Gephyrotox- in 287C (1983) (Scheme 14) P 3.2.4. Saegusa’s Formal Synthesis of (±)-Ge- phyrotoxin 287C (1983) (Scheme 15) Q 3.2.5. Pearson’s Formal Synthesis of (±)-Ge- phyrotoxin 278C (2000) (Scheme 16) R 3.2.6. Hsung’s Formal Synthesis of (+)-Gephyr- otoxin 278C (2001) (Scheme 17) R 3.2.7. Lhommet’s Formal Synthesis of (+)-Ge- phyrotoxin 278C (2008) (Scheme 18) S 3.2.8. Trudell’s Formal Synthesis of (+)-Gephyr- otoxin 278C (2010) (Scheme 19) S 3.2.9. Spino’s Formal Synthesis of (-)-Gephyr- otoxin 278C (2010) (Scheme 20) T 3.2.10. Sato and Chida’s Synthesis of (±)-Ge- phyrotoxin 287C (2014) (Scheme 21) T 3.2.11. Smith’s Synthesis of (-)-Gephyrotoxin 287C (2014) (Scheme 22) U 3.2.12. Gephyrotoxin 287C Conclusion V 3.3. Agelastatin A V 3.3.1. Weinreb’s Synthesis of (±)-Agelastatin A (1999) (Scheme 23) V 3.3.2. Feldman’s Synthesis of (-)-Agelastatin A (2002) (Scheme 24) W 3.3.3. Hale’s Synthesis of (-)-Agelastatin A (2004) (Scheme 25) X 3.3.4. Davis’s Synthesis of (-)-Agelastatin A (2005/2009) (Scheme 26) Y 3.3.5. Trost’s Synthesis of (+)-Agelastatin A and Formal Synthesis of (-)-Agelastatin A (2006/2009) (Scheme 27) Z 3.3.6. Ichikawa’s Synthesis of (-)-Agelastatin A (2007) (Scheme 28) AA 3.3.7. Yoshimitsu and Tanaka’s Synthesis of (-)-Agelastatin A (2008) (Scheme 29) AB 3.3.8. Wardrop’s Synthesis of (±)-Agelastatin A (2009) (Scheme 30) AC 3.3.9. Du Bois’s Synthesis of (-)-Agelastatin A (2009) (Scheme 31) AC 3.3.10. Chida’s Synthesis of (-)-Agelastatin A (2009) (Scheme 32) AD 3.3.11. Movassaghi’s Synthesis of (-)-Agelas- tatin A (2010) (Scheme 33) AE 3.3.12. Romo’s Synthesis of (±)-Agelastatin A (2012) AG 3.3.13. Batey’s Synthesis of (±)-Agelastatin A (2013) (Scheme 36) AG 3.3.14. Agelastatin A Conclusion AI 3.4. Citrinadin B AI 3.4.1. Wood’s Synthesis of (+)-Citrinadin B (2013) (Scheme 37) AI Special Issue: 2015 Frontiers in Organic Synthesis Received: March 16, 2015 Review pubs.acs.org/CR © XXXX American Chemical Society A DOI: 10.1021/acs.chemrev.5b00154 Chem. Rev. XXXX, XXX, XXX-XXX