Part I. General approach to the total synthesis of 9-methoxy substituted indole alkaloids: Total synthesis of the opioid agonistic indole alkaloid, mitragynine as well as 9-methoxy-geissoschizol and 9-methoxy-N(b)-methylgeissoschizol. Part II. Studies to

Part 1. An efficient synthetic route to the optical active 4-methoxytryptophan ethyl ester 45 on multigram scale has been developed. The 4-methoxy-3-methylindole 87 and the isomeric indoline derivative 88 were synthesized via the Mori-Ban-Hegedus indole synthesis. The ethyl ester of (D)-4-methoxytryptophan 97 was obtained in 98% ee with the radical-mediated regioselective bromination of indoline 88 served as a key step. Alternatively, this 4-methoxytryptophan 97 could be synthesized by the Larock heteroannulation of the aryl iodide 86 and the internal alkyne 52. The Boc protection of the aniline was crucial to the success of this heteroannulation.; The alpha,beta-unsaturated ester 47 was synthesized with the Pictet-Spengler reaction as the key asymmetric step. This was followed by the Ni(COD)2 mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 46 was removed to provide the key intermediate 45. This tetracyclic ester 45 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol 42 and 9-methoxy-Nb-methylgeissoschizol 43 as well as the opioid agonistic alkaloid mitragynine 3.; Part II. The aldehyde 168 has been synthesized in 48.7% yield from the methyl pyruvate 171 via Claisen rearrangement and ozonolysis. The advanced intermediate 161 was synthesized in 47.3% overall yield for 5 steps starting from tryptamine 169. The Pictet-Spengler reaction and the TMSOTf/lutidine mediated cyclization severed as key reactions. The radical-mediated cyclization of this key intermediate 161 was not successful and the reduction of the vinyl halide was observed. The Ni(COD)2 and Pd(OAc) 2 mediated cyclization only led to the dealkylation product 179 . The intramolecular Heck coupling of the allyl alcohol 165 was attempted, although no cyclization was observed. The reluctance of the cyclization of the key intermediate 161 and 165 was due to the strain present in the cup-shaped pleiocarpamine skeleton.; The tetracyclic ester 188 has been synthesized from D-tryptophan with the asymmetric Pictet-Spengler reaction and Ni(COD)2 mediated cyclization served as the key steps. The alpha-hydroxyester 203 of the carbamate 202 was achieved employing the chiral Davis Oxaziridine. The attempt of the removal of the Boc moiety and the cyclization of the tosylate 203 in refluxing xylene was not successful.