Studies in sigmatropic rearrangements of N-prenylindole derivatives--a formal enantiomerically pure synthesis of tryprostatin B.
Rearrangement of N(a)-prenyl-N(b)-acetyltryptamine, induced by BF3.Et2O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, N(a)-prenyl-N(b)-phthaloyl-l-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF3 to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol(-1).
Cardoso
A Sofia P
AS
Chemistry Department, REQUIMTE/CQFB, Faculty of Sciences and Technology, New University of Lisbon, 2829-516, Monte de Caparica, Portugal.
Marques
M Manuel B
MM
Srinivasan
Natarajan
N
Prabhakar
Sundaresan
S
Lobo
Ana M
AM
Rzepa
Henry S
HS
D002384:Catalysis; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; C097859:tryprostatin B