951327-91-6Relevant articles and documents
General approach to the total synthesis of 9-methoxy-substituted indole alkaloids: Synthesis of mitragynine, as well as 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol
Ma, Jun,Yin, Wenyuan,Zhou, Hao,Liao, Xuebin,Cook, James M.
experimental part, p. 264 - 273 (2009/04/10)
(Chemical Equation Presented) Herein, the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3), and 9-methoxy-Nb-methylgeissoschizol (4) are described. Initially, an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of D-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc-protected aniline 10b was crucial to the success of this heteroannulation. The α,β-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)2-mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-N b-methylgeissoschizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1).
