Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 12, 2014
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: (-)-L-Batzellaside A (Toyooka), Limazepine A (Zemribo), (+)-Febrifugine (Pansare), Amathaspiramide F (Tambar), Allomatrine (Brown), Lyconadine C (Waters), Tabersonine (Andrade)

Naoki Toyooka of the University of Toyama prepared (Eur. J. Org. Chem. 2013, 2841. DOI: 10.1002/ejoc.201201567) the lactam 1 from commercial tri-O-benzyl-D-glucal. Reduction with Dibal followed by coupling of the intermediate with allyltrimethylsilane delivered the piperidine 2, that was carried on to (-)-L-Batzellaside A (3).

Ronalds Zemribo of the Latvian Institute of Organic Synthesis effected (Org. Lett. 2013, 15, 4406. DOI: 10.1021/ol4019453) Ireland-Claisen rearrangement of the lactone 4 to give the pyrrolidine 5 with high geometric control. This was readily converted to Limazepine E (6).

Sunil V. Pansare of Memorial University used (Synthesis 2013, 45, 1863. DOI: 10.1055/s-0033-1338706) an organocatalyst to set the relative and absolute configuration of 9. The acyclic stereogenic center of 9 was inverted twice en route to (+)-Febrifugine (10).

Uttam K. Tambar of UT Southwestern Medical Center combined (Org. Lett. 2013, 15, 5138. DOI: 10.1021/ol4025937) 11 with 12 under Pd catalysis to set the relative configuration of 13. Late-stage bromination completed the synthesis of Amathaspiramide F (14).

Richard C. D. Brown of the University of Southampton used (Org. Lett. 2013, 15, 4596. DOI: 10.1021/ol402198n) the sulfinylimine of 15 to direct the stereochemical sense of the addition of 16. The product 17 was carried over several steps to the tetracyclic alkaloid Allomatrine (18).

Stephen P. Waters of the University of Vermont devised (Org. Lett. 2013, 15, 4226. DOI: 10.1021/ol401954f) what appears to be a general route to pyridones. On warming, the acyl azide derived from the acid 19 rearranged to the isocyanate, that cyclized to the pyridone 20. Deprotection led to the Lycopodium alkaloid Lyconadin C (21).

Among the several creative routes to indole alkaloids that have been put forward in recent months, the synthesis of Tabersonine (25) (J. Am. Chem. Soc. 2013, 135, 13334. DOI: 10.1021/ja408114u) by Rodrigo B. Andrade of Temple University stands out. Deprotonation of 22 led to an anion that was condensed with 23 to give 24, with the relative and absolute configuration directed by the pendant sulfinylimine. In addition to Tabersonine, the intermediate 24 was carried on to Vincadifformine and to Aspidospermidine.

D. F. Taber, Org. Chem. Highlights 2014, May 12.