- Synthesis of (-)-Melodinine K: A Case Study of Efficiency in Natural Product Synthesis
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Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count and scale. The execution of a natural product synthesis, that is, the sum and identity of each reaction employed therein, falls along a continuum of chemical (abiotic) synthesis on one extreme, followed by the hybrid chemoenzymatic approach, and ultimately biological (biosynthesis) on the other, acknowledging the first synthesis belongs to Nature. Starting materials also span a continuum of structural complexity approaching the target with constituent elements on one extreme, followed by petroleum-derived and "chiral pool"building blocks, and complex natural products (i.e., semisynthesis) on the other. Herein, we detail our approach toward realizing the first synthesis of (-)-melodinine K, a complex bis-indole alkaloid. The total syntheses of monomers (-)-tabersonine and (-)-16-methoxytabersonine employing our domino Michael/Mannich annulation is described. Isolation of (-)-tabersonine from Voacanga africana and strategic biotransformation with tabersonine 16-hydroxylase for site-specific C-H oxidation enabled a scalable route. The Polonovski-Potier reaction was employed in biomimetic fragment coupling. Subsequent manipulations delivered the target. We conclude with a discussion of efficiency in natural products synthesis and how chemical and biological technologies define the synthetic frontier.
- Walia, Manish,Teijaro, Christiana N.,Gardner, Alex,Tran, Thi,Kang, Jinfeng,Zhao, Senzhi,O'Connor, Sarah E.,Courdavault, Vincent,Andrade, Rodrigo B.
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p. 2425 - 2433
(2020/09/01)
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- Synthesis of vinca alkaloids and related compounds. 100. Stereoselective oxidation reactions of compounds with the aspidospermane and quebrachamine ring system. First synthesis of some alkaloids containing the epoxy ring
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The first syntheses of the alkaloids (-)-mehranine (3), (+)-voaphylline/conoflorine (4), (+)-Na-methylvoaphylline/hecubine (5), and (-)-lochnericine (2) were achieved by stereoselective epoxidation starting from (-)-tabersonine (1), through intermediates with the aspidospermane and quebrachamine skeleton.
- Eles, Janos,Kalaus, Gyoergy,Greiner, Istvan,Kajtar-Peredy, Maria,Szabo, Pal,Keseru, Gyoergy Miklos,Szabo, Lajos,Szantay, Csaba
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p. 7255 - 7260
(2007/10/03)
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- Biotransformation of tabersonine in cell suspension cultures of Catharanthus roseus.
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To investigate the reactions involved in the biosynthesis of vindoline from tabersonine, the bioconversion products formed when the latter compound was fed to cell suspension cultures of Catharanthus roseus were isolated and characterized. Two biotransformation products of tabersonine were isolated and shown to be lochnericine, which is formed by epoxidation of tabersonine at positions 14, 15, and lochnerinine, the 11-methoxylation product of lochnericine. The bioconversion ratio of the main biotransformation product, lochnericine, reached a value of 80.6% within three days.
- Furuya,Sakamoto,Iida,Asada,Yoshikawa,Sakai,Aimi
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p. 3065 - 3068
(2007/10/02)
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