Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues

• Published in: Journal of organic chemistry Vol. 80; no. 16; pp. 8046 - 8054
• Main Authors: Wauters, I, Goossens, H, Delbeke, E, Muylaert, K, Roman, B. I, Van Hecke, K, Van Speybroeck, V, Stevens, C. V
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.08.2015; Amer Chemical Soc
• Subjects: Breast Neoplasms - chemistry; Breast Neoplasms - drug therapy; Chemistry; Chemistry, Organic; Diketopiperazines - chemistry; Female; Humans; Indole Alkaloids - chemical synthesis; Indole Alkaloids - chemistry; Indole Alkaloids - pharmacology; Models, Molecular; Molecular Conformation; Neoplasm Proteins - antagonists & inhibitors; Physical Sciences; Quantum Theory; Science & Technology; Stereoisomerism; Structure-Activity Relationship; MECHANISM; TRYPROSTATIN-B; CHEMISTRY; NITROGEN; INHIBITORS; TADALAFIL; MULTIDRUG-RESISTANCE; EPIBATIDINE ANALOGS; DERIVATIVES; REVERSAL
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b01161

A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan–proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C–C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity.