New Strategies for the Synthesis of Monoterpene Indole Alkaloids

Abstract

The synthetic efforts of the author's research team in several areas within the monoterpene indole alkaloid family are summarized. Most of the work was accomplished in the field of the Aristotelia alkaloids, where some 25 natural products were synthesized for the first time. Systematic investigations on the oxidative rearrangement of indoles to oxindoles and pseudoindoxyl derivatives led to control over the chemoselectivity and stereoselectivity of this process, which served for enantioselective preparations of the simple alkaloids horsfiline and elacomine. In addition, recent developments in a novel approach to Iboga alkaloids containing a hydroxyl group at C(19) are presented. The key steps involved a self-immolating 1,4-chirality transfer in an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin [2+3]-cycloaddition to give the aliphatic isoquinuclidine core of the target molecules. The first synthesis of (19R)hydroxyibogamine was completed by grafting a 3-ethylindole unit onto the aliphatic nitrogen, followed by closing the 7membered ring.

Progress in the Synthesis of Iboga-alkaloids and their Congeners

“…In 2006, Borschberg's group reported the first enantioselective synthesis of (−)-(19R)-ibogamin-19-ol. 4,54 The key intermediate 90 54,55 was synthesized in optically active form starting from L-glutamic acid and (2S)-but-3-en-2-ol. The synthesis of 90 shown in (Scheme 8) involves two key steps, an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin 1,3-dipolar cycloaddition reaction.…”

Synthesis and Functionalization of Indoles through Rhodium-Catalyzed Reactions

“…This tandem approach includes three steps, the in situ generation of oxo aldehyde, its conversion to aryl hydrazones, and the [3,3]-sigmatropic rearrangement to the final indole 137. Beller and co-workers [89] used the Rh/Iphos catalyst system to prepare substituted indoles (140) from olefins (138) synthesis of 3-methyl indole (144) under hydroformylation conditions using supported rhodium as catalyst.…”

“…Akao, and co-workers [96] have developed a highly effective, and chemo selective method of preparing substituted indoles (149a) along with very small amount of the byproduct (1 4 9 b ) from (E )-2-nitropyrrolidinostyrenes (1 4 8 ) v i a hydrogenation in the presence of a rhodium catalyst doped by additives such as Ni(NO 3 ) 2 .6H 2 O, Fe(OAc) 2 or Co(acac) 3 . Additives play a very important role in the formation of the product (149a) and it reduces the formation of byproduct to negligible amount (1-3 %) in the reaction.…”

“…During this period, the recognition of plant growth hormone, heteroauxin, and essential amino acid tryptophan as the derivatives of indole have added stimulus to the indole research. Indoles, both naturally-occurring, and synthetic are of immense importance as biologically active alkaloids, and pharmaceutical agents [1][2][3][4]. Despite the intense scrutiny that indoles have undergone for the past 100 years, the investigation of chemistry of this fascinating heterocycle has been continued to be one of the most important areas of heterocyclic chemistry.…”

Research Progress of Synthesis of Bis(indolyl)methanes

“…1957 年出版的《生物碱大全》共收集了 4030 种化合物, 其中含有吲哚环的生物碱占 1/5 [1,2] , 这类化合物具有很 好的药理活性 [3] 和生物活性 [4] , 其抗菌、 抗氧化等活性被 应用于抗生素药物中 [5] . 作为诸多陆地和海洋生物代谢 产物 [6,7] 的双吲哚甲烷类衍生物具有更为丰富的生理活 性 [8,9] , 主要用于抗菌 [10] 、治疗纤维肌痛、长期疲劳、急 性肠炎 [11,12] 、促进人体内的雌性激素的代谢 [13] 、能有效 的抑制癌细胞的增长 [14,15] , 尤其对乳腺癌细胞的增长具 有很好的抑制活性 [16,17] .…”