ChemInform Abstract: A First Generation Total Synthesis of (+)-Salicylihalamide A.

Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products.1 Introduction2 Synthetic Strategy2.1 First Generation2.2 Second Generation2.3 Third Generation2.3.1 Radical Endgame2.3.2 Completion of the Total Synthesis3 Conclusion

Download Full-text

Evolution of a Chemical Strategy Toward the Synthesis of Unsymmetrically Oxidized Nuphar Alkaloids

Synlett ◽

10.1055/s-0037-1611866 ◽

2019 ◽

Vol 30 (14) ◽

pp. 1632-1642

Author(s):

Jacob J. Lacharity ◽

Armen Zakarian

Keyword(s):

Total Synthesis ◽

First Generation ◽

Second Generation ◽

Third Generation ◽

Successful Strategy ◽

Synthesis Design ◽

Sulfonium Ylide ◽

Chemical Strategy

Here we describe the frustrations, joys, and unexpected turns experienced in our journey toward a successful strategy directed at the total synthesis of unsymmetrically oxidized Nuphar thioalkaloids. While many adjustments were made to our initial synthesis plan, our general approach to the construction of the central bis(spirothiolane) moiety remained unchanged. Specifically, each iteration of our synthesis design involved the formation of the thiaspirane motif through the stereodivergent coupling of a thietane with a metal carbenoid, followed by a Stevens-type rearrangement of the resulting sulfonium ylide.1 Introduction2 First-Generation Strategy3 Second-Generation Strategy4 Third-Generation Strategy5 Conclusion

Download Full-text

Lessons from the total synthesis of (±)-phalarine: Insights into the mechanism of the Pictet–Spengler reaction

Pure and Applied Chemistry ◽

10.1351/pac-con-09-11-14 ◽

2010 ◽

Vol 82 (9) ◽

pp. 1735-1748 ◽

Cited By ~ 11

Author(s):

John D. Trzupek ◽

Chaomin Li ◽

Collin Chan ◽

Brendan M. Crowley ◽

Annekatrin C. Heimann ◽

...

Keyword(s):

Natural Products ◽

Total Synthesis ◽

First Generation ◽

Capture Reaction ◽

Structural Framework

The furanobisindole alkaloid, phalarine, possesses a unique structural framework within the alkaloid family of natural products. Our laboratory recently disclosed the racemic total synthesis of phalarine, featuring an efficient azaspiroindolenine rearrangement; this achievement is revisited in detail. Upon completion of the first-generation total synthesis, we explored some interesting mechanism-level issues with regard to the key azaspiroindolenine rearrangement. These investigations provided valuable insights into the mechanism of racemization during the azaspiroindolenine rearrangement en route to synthetic phalarine. In addition, in the course of these studies, we demonstrated the Pictet–Spengler capture reaction for C2-aryl indoles, and successfully isolated the elusive azaspiroindolenine intermediate of the Pictet–Spengler reaction. Key insights into the remarkably subtle stereoelectronics that govern this rearrangement for C2-arylated indoles are discussed.

Download Full-text