Explorations on the total synthesis of the unusual marine alkaloid chartelline A.
In work directed toward a total synthesis of chartelline A (1a), a strategy was investigated to construct the 10-membered ring of this marine alkaloid via an intramolecular aldehyde/beta-lactam cyclocondensation to form the macrocyclic enamide functionality. Therefore, spiro-beta-lactam and imidazole fragments were first prepared. Tribromooxindole beta-lactam 24 was synthesized from commercially available 5-nitroisatin (18) in seven steps and 30% overall yield via a Staudinger ketene-imine [2 + 2]-cycloaddition strategy. The requisite 2-bromoimidazole subunit 40 bearing a terminal alkyne and a masked aldehyde was efficiently prepared from the readily available imidazole ester 25 in 10 steps. With both advanced intermediates available, the addition of the lithium acetylide generated from 2-bromoimidazole subunit 40 to the gamma-lactam carbonyl group of N-Boc-tribromooxindole 24 was investigated, affording the desired N-Boc-aminal 41. Hydrolysis of the acetonide moiety of 41, followed by oxidative cleavage of the resulting diol, gave the aldehyde 42. Unfortunately, treatment of aldehyde 42 with p-toluenesulfonic acid did not give the desired 10-membered macrocyclic (Z)-enamide 46, but rather the highly unsaturated seven-membered ring compound 44.
Sun
Cuixiang
C
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Lin
Xichen
X
Weinreb
Steven M
SM
D000818:Animals; D001966:Bromine / Q000737:chemistry; D002013:Bryozoa / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009792:Oceans and Seas; D047090:beta-Lactams / Q000737:chemistry
D007093:Imidazoles; D007211:Indoles; D047090:beta-Lactams; C513615:chartelline; D001966:Bromine