B.I. Roman

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

Chemistry - A European Journal

80 (16), 8046-8054

2015

A1

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.

DOI

http://dx.doi.org/10.1021/acs.joc.5b01161

Synthesis of Tricyclic Phosphonopyrrolidines via IMDAF: Experimental and Theoretical Investigation of the Observed Stereoselectivity

D.D. Claeys, K. Moonen, B.I. Roman, V.N. Nemykin, V.V. Zhdankin, M. Waroquier, V. Van Speybroeck, C.V. Stevens

Journal of Organic Chemistry

73 (20), 7921-7927

2008

A1

Abstract

During the synthesis of tricyclic phosphonopyrrolidines via intramolecular Diels−Alder reactions of 1-acylamino(furan-2-yl)methyl phosphonates, two isomers are formed in most cases. The presence of a short three-atom tether together with spectroscopic data, including difference NOE, revealed that the cycloaddition occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via X-ray analysis. A thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically. Density functional theory methods and several high-level post Hartree−Fock procedures were used to rationalize the observed isomer ratio of the IMDAF-reactions. This was done for two different types of reagents: with the activating carbonyl group in the tether or as a substituent on the tether. For the first type of molecules there is a large steric hindrance of the bulky tether substituents that disfavors the exo-isomer. In the latter case, there was a very small energy difference between the transition states causing a mixture of epimers being formed.

DOI

http://dx.doi.org/10.1021/jo801138s

Experimental and computational study of the ring opening of tricyclic oxanorbornenes to polyhydro isoindole phosphonates

D.D. Claeys, C.V. Stevens, B.I. Roman, P. Van De Caveye, M. Waroquier, V. Van Speybroeck

Organic & Biomolecular Chemistry

8, 3644-3654

2010

A1

Abstract

Phosphonylated azaheterocycles are an important class of compounds with high biological potential as conformationally restricted bioisosteres of amino acids. Therefore, it is of interest to synthesize conformationally constrained amino phosphonates. We wanted to investigate possible routes via ring opening of α-amino phosphonates with an oxanorbornene skeleton, as these can be synthesized with high stereoselectivity. This was achieved using different Lewis acids, leading to a range of products. The reaction with TiCl4 and FeCl3 was modelled at a DFT level of theory to get insight in the pathways towards the corresponding products. To ease the work up, the Fe(III) catalyst was coated on montmorillonite clay, but this accelerated aromatization after ring opening. Quenching the FeCl3 catalyzed reaction mixture on celite caused complete aromatization.