The naturally occurring compound 3,6-bis-(5-chloro-2-piperidyl)-2,5-piperazinedione (1) is a promising new antitumor drug. The mechanisms of action of antitumor alkylating agents, particularly the nitrogen mustards and sesquiterpene lactones, suggest possible modes of antitumor activity of compound 1. A possible synthetic scheme for compound 1 is developed by consideration of methods of synthesis of piperidines, (alpha)-substituted-(alpha),(beta)-unsaturated esters, and (beta)-amino alcohols. / A synthesis of (alpha)-chloro-(alpha),(beta)-unsaturated esters from carbonyl compounds and t-butyl (alpha)-chloro-(alpha)-trimethylsilyl acetate is developed. Oxyamination of the terminal double bond of t-butyl 2-chloro-2,6-heptadienoate occurs by epoxidation and reaction with an amine or azide ion and by osmium tetroxide catalyzed reaction with Chloramine-T. The piperidine ring is formed by an internal Michael raction of t-butyl 2-chloro-6-t-butyldimethylsilyloxy-7-tosylamino-2-heptenoate. The amino acid (1-tosyl-5-hydroxy-2-piperidyl) glycine is synthesized and found to be unstable to acidic esterification conditions. / Strategies for overcoming the problems encountered in the synthesis are discussed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68506 |
| Date | January 1979 |
| Creators | Moreland, Margaret. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000088682, proquestno: AAINK50517, Theses scanned by UMI/ProQuest. |
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