Total Synthesis of the Kopsia lapidilecta Alkaloid (±)-Lapidilectine B

• Published in: Journal of organic chemistry Vol. 69; no. 26; pp. 9109 - 9122
• Main Authors: PEARSON, William H., LEE, Ill Young, MI, Yuan, STOY, Patrick
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.12.2004; Amer Chemical Soc
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Apocynaceae - chemistry; Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Indoles - chemical synthesis; Indoles - chemistry; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Spectrum Analysis; HIGHER-ORDER; (+/-)-LAHADININE-B; CYCLOADDITIONS; TRANSMETALATION; 2-AZAALLYL ANIONS; PAUCIFLORINE; (+/-)-KOPSIDASINE; INDOLE ALKALOIDS; CYCLIZATION; LEPADIFORMINE; Intramolecular reaction; Acetylenic compound; Organic azide; Nitrogen heterocycle; Natural product; Lactone; SN2 mechanism; Oxygen heterocycle; Pyrrolidine derivatives; Spiran; Organic sulfide; Total synthesis; Eight membered ring; Alkaloid; Cycloaddition; Lithium Organic compounds; Cyclization; Vinylic compound; Indole derivatives; Chemical synthesis; Enolate
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048917u

The total synthesis of Kopsia lapidilecta alkaloid (+/-)-lapidilectine B is described. Notable elements of this synthesis include the first natural products application of the Smalley azido-enolate cyclization to form the 1,2-dihydro-3H-indol-3-one (indoxyl) core and installation of the pyrrolidine ring by a 2-azaallyllithium [3+2] cycloaddition with the acetylene equivalent phenyl vinyl sulfide. Closure of the eight-membered perhydroazocine ring is accomplished via the intramolecular S(N)2 substitution of a mesylate. This constitutes the first synthesis of a member of the 5,6,12,13-tetrahydro-11a,13a-ethano-3H-pyrrolo[1',2':1,8]azocino[5,4-b]indole class of alkaloids.