{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/150563"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/150563","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Total Synthesis of Oligomeric Cyclotryptamine Alkaloids","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_html":"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_has_math":false,"creators":["Scott, Tony Z."],"institution":"Massachusetts Institute of Technology","degree_name":"Doctoral","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Chemistry","school":null,"contributors":[],"advisors":["Movassaghi, Mohammad"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-02","date_published":"2023-02","updated_at":"2026-07-22T22:21:44Z","subjects":[],"languages":[],"rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"rights_urls":["http://rightsstatements.org/page/InC-EDU/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1721.1/150563","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Movassaghi, Mohammad"]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. 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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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Total Synthesis of Oligomeric Cyclotryptamine Alkaloids"]}]}],"canonical_facts":{"dc:contributor.advisor":["Movassaghi, Mohammad"],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Chemistry"],"dc:creator":["Scott, Tony Z."],"dc:date.accessioned":["2023-04-25T14:22:02Z"],"dc:date.available":["2023-04-25T14:22:02Z"],"dc:date.issued":["2023-02"],"dc:description.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."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/150563"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"dc:rights.uri":["http://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Total Synthesis of Oligomeric Cyclotryptamine Alkaloids"],"dc:type":["Thesis"],"thesis:degree_name":["Doctoral","Doctor of Philosophy"]},"updated_at":"2026-07-22T22:21:44Z"}