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Synthesis 2007(7): 1047-1053  
DOI: 10.1055/s-2007-965962
PAPER
© Georg Thieme Verlag Stuttgart · New York

Simple Approach to Highly Functionalized Trisubstituted Tetrahydro­pyrimidine-2,4-diones from Perhydropyrazino[1,2-f]pyrimidine-3,6,8-trione Precursors

Rosario Patiño-Molinaa,b, M. Teresa García-Lópeza, Edurne Cenarruzabeitiac, Joaquín Del Ríoc, Rosario González-Muñiz*a
a Instituto de Química Médica-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34(91)5644853; e-Mail: iqmg313@iqm.csic.es;
b Escuela Técnica Superior de Ingenieros Industriales, Universidad de Valladolid, Paseo del Cauce s/n, 4701 Valladolid, Spain
c Departamento de Farmacología-Unidad Asociada al CSIC, Universidad de Navarra, Irunlarrea 1, 31080 Pamplona, Spain
Further Information

Publication History

Received 3 November 2006
Publication Date:
28 February 2007 (online)

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Abstract

Unprecedented trisubstituted tetrahydropyrimidine-2,4-diones were easily synthesized in two steps involving Boc-amide protection and controlled ring opening, from perhydropyrazino[1,2-f]pyrimidine-3,6,8-triones. These bicyclic derivatives were prepared by reaction of 2-oxopiperazines derived from dipeptides with isocyanates, followed by cyclization. The monocyclic pyrimidinone derivatives were further elaborated to potential CCK ligands that have contributed to a better understanding of the structural requirements for efficient binding at the CCK1 receptor.

Key words

heterocycles - peptides - bicyclic compounds - ring opening - medicinal chemistry

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18

An authentic sample of compound 19b, prepared by an alternative stereospecific synthetic route, allows the unequivocal assignment of the configuration at C6 in the diastereoisomeric pairs 19a,b and 20a,b: Patiño-Molina, R.; Cubero, J.; Pérez de Vega, M. J.; García-López, M. T.; González-Muñiz, R., unpublished results.

19

The increased shielding (Δβ = δ19b - δ21b) was 0.36 ppm for the H-5eq and 1.67 ppm for the H-5ax.