Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues

I Wauters; H Goossens; E Delbeke; K Muylaert; B I Roman; K Van Hecke; V Van Speybroeck; C V Stevens

doi:10.1021/acs.joc.5b01161

Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues

J Org Chem. 2015 Aug 21;80(16):8046-54. doi: 10.1021/acs.joc.5b01161. Epub 2015 Aug 3.

Authors

I Wauters¹, H Goossens², E Delbeke¹, K Muylaert¹, B I Roman¹, K Van Hecke³, V Van Speybroeck², C V Stevens¹

Affiliations

¹ †Research Group SynBioC, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
² ‡Center for Molecular Modelling, Ghent University, Technologiepark 903, 9000 Ghent, Belgium.
³ §XStruct, Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281, S3, 9000 Ghent, Belgium.

PMID: 26193166
DOI: 10.1021/acs.joc.5b01161

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / chemistry
Breast Neoplasms / drug therapy*
Diketopiperazines / chemistry*
Female
Humans
Indole Alkaloids / chemical synthesis
Indole Alkaloids / chemistry
Indole Alkaloids / pharmacology*
Models, Molecular
Molecular Conformation
Neoplasm Proteins / antagonists & inhibitors*
Quantum Theory
Stereoisomerism
Structure-Activity Relationship

Substances

Diketopiperazines
Indole Alkaloids
Neoplasm Proteins
brevianamide F