2026-09-20T17:49:38Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1505632023-04-26T03:25:13Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Movassaghi, Mohammad
Scott, Tony Z.
Massachusetts Institute of Technology. Department of Chemistry
2023-04-25T14:22:02Z
2023-04-25T14:22:02Z
2023-02
2023-04-05T18:52:52.827Z
https://hdl.handle.net/1721.1/150563
I. Total Synthesis and Stereochemical Assignment of (–)-Psychotridine
We report the first enantioselective total synthesis and stereochemical assignment of (–)-psychotridine. The application of our diazene-directed assembly of enantiomerically enriched cyclotryptamines afforded a highly convergent synthesis of the pentameric alkaloid, allowing its detailed structural assignment. Highlights of the synthesis include the introduction of four quaternary stereocenters with complete stereochemical control in a single step via the photoextrusion of three molecules of dinitrogen from an advanced intermediate and metal-catalyzed C–H amination reactions in challenging settings.
II. Iterative, Diazene-Directed Total Synthesis of (+)-Quadrigemine H, (+)-Isopsychotridine C, (+)-Oleoidine, and (+)-Caledonine
We describe the unified enantioselective total synthesis of the polycyclotryptamine natural products (+)-quadrigemine H, (+)-isopsychotridine C, (+)-oleoidine, and (+)-caledonine. Our bioinspired synthesis leverages the modular, diazene-directed assembly of whole cyclotryptmines to iteratively introduce C3a−C7' quaternary linkages on an advanced heterodimeric intermediate with full stereochemical control at each quaternary linkage. We developed a strategy for iterative aryl-alkyl diazene synthesis using increasingly complex oligomeric hydrazide nucleophiles and bifunctional cyclotryptamines bearing a C3a leaving group and a pendant C7 pronucleophile. The utility of our method is demonstrated by the first total synthesis of heptamer (+)-caledonine and hexamer (+)-oleoidine. Additionally, enabled by our fully stereoselective total synthesis and acquisition of expanded characterization data, we provide the first complete stereochemical assignment of pentamer (+)-isopsychotridine C and confirm that tetramer (+)-quadrigemine H is identical to the alkaloid called (+)-quadrigemine I.
Ph.D.
Massachusetts Institute of Technology
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http://rightsstatements.org/page/InC-EDU/1.0/
Total Synthesis of Oligomeric Cyclotryptamine Alkaloids
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<Abstract>I. Total Synthesis and Stereochemical Assignment of (–)-Psychotridine
We report the first enantioselective total synthesis and stereochemical assignment of (–)-psychotridine. The application of our diazene-directed assembly of enantiomerically enriched cyclotryptamines afforded a highly convergent synthesis of the pentameric alkaloid, allowing its detailed structural assignment. Highlights of the synthesis include the introduction of four quaternary stereocenters with complete stereochemical control in a single step via the photoextrusion of three molecules of dinitrogen from an advanced intermediate and metal-catalyzed C–H amination reactions in challenging settings.
II. Iterative, Diazene-Directed Total Synthesis of (+)-Quadrigemine H, (+)-Isopsychotridine C, (+)-Oleoidine, and (+)-Caledonine
We describe the unified enantioselective total synthesis of the polycyclotryptamine natural products (+)-quadrigemine H, (+)-isopsychotridine C, (+)-oleoidine, and (+)-caledonine. Our bioinspired synthesis leverages the modular, diazene-directed assembly of whole cyclotryptmines to iteratively introduce C3a−C7' quaternary linkages on an advanced heterodimeric intermediate with full stereochemical control at each quaternary linkage. We developed a strategy for iterative aryl-alkyl diazene synthesis using increasingly complex oligomeric hydrazide nucleophiles and bifunctional cyclotryptamines bearing a C3a leaving group and a pendant C7 pronucleophile. The utility of our method is demonstrated by the first total synthesis of heptamer (+)-caledonine and hexamer (+)-oleoidine. Additionally, enabled by our fully stereoselective total synthesis and acquisition of expanded characterization data, we provide the first complete stereochemical assignment of pentamer (+)-isopsychotridine C and confirm that tetramer (+)-quadrigemine H is identical to the alkaloid called (+)-quadrigemine I.</Abstract>
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