Organic Chemistry Portal
Organic Chemistry Highlights

Search Org. Chem. Highlights:

Match: or and

Monday, November 26, 2012
Tristan H. Lambert
Columbia University

Alkaloid Synthesis: Indolizidine 207A (Shenvi), (-)-Acetylaranotin (Reisman), Flinderole A (May), Isohaouamine B (Trauner), (-)-Strychnine (MacMillan)

Ryan A. Shenvi at the Scripps Research Institute in La Jolla has reported (J. Am. Chem. Soc. 2012, 134, 2012. DOI: 10.1021/ja211090n) a procedure for the stereoselective formal hydroamination of aminodienes to produce indolizidines. The procedure involves an amine-directed hydroboration, followed by a B to N bond migration (cf. 2) that is induced with molecular iodine and sodium methoxide. The pyrrolidinyl alcohols 3 generated upon oxidation can then be converted by Mitsunobu reaction to the target bicyclic structures, including indolizidine 207A.

Jeremy A. May at the University of Houston has shown (J. Am. Chem. Soc. 2012, 134, 6936. DOI: 10.1021/ja301387k) that a biomimetic strategy to access members of the flindersial alkaloids is viable. Borrerine can be prepared in two steps from tryptamine and subsequently dimerized by treatment with acid. Notably, the exclusive formation of either flinderoles A and C or isoborreverine can be achieved by treatment with either acetic acid or BF3•OEt2 respectively. The different outcomes of these dimerizations are the result of competing formal [3+2] and [4+2] cycloaddition pathways.

The unusual paracyclophane-containing alkaloid haouamine B has undergone (J. Am. Chem. Soc. 2012, 134, 9291. DOI: 10.1021/ja301326k) a structural revision by Eva Zubia at the University of Cádiz thanks to the total synthesis of the reported structure (now called isohaouamine B) by Dirk Trauner at the University of Munich. To construct the strained paracyclophane moiety, the iodo amine 4 was deprotected and cyclized to produce structure 5. Aromatization of the cyclohexenone ring then provided the energetic offset for the strain present in 6. This route provided useful quantities of isohaouamine B for biological testing.

Few natural products have captured the imaginations of chemists more than strychnine, and some of the most impressive achievements in the field of total synthesis have come from those who have taken up this challenge. David W. C. MacMillan at Princeton University has designed (Nature 2011, 475, 183. DOI: 10.1038/nature10232) an enantioselective approach that not only furnishes (-)-strychnine in 12 steps, but also provides rapid access to a range of other biosynthetically related yet structurally diverse alkaloids, including (-)-akuammicine, (+)-aspidospermidine, (+)-vincadifformine, and (-)-kopsanone. Each of these total syntheses proceeds through a common intermediate 9 that is constructed by an organocatalytic cascade that merges the selenoindole 7 and propiolaldehyde. The idea of the “collective synthesis” of natural products may prove useful for the preparation of useful quantities of complex structures via common intermediates.

T. H. Lambert, Org. Chem. Highlights 2012, November 26.