THE CONFORMATION OF NEW TETRAHYDROPYRIMIDINE DERIVATIVES IN SOLUTION AND IN THE CRYSTAL

We have recently identified by NMR techniques two new tetrahydropyrimi dine derivatives, l-4-carboxy-5-hydroxy-3,4,5,6-tetrahydropyrimidine [ THP(A)] and 2-methyl-4-carboxy-3,4,5,6-tetrahydropyrimidine [THP(B)], which accumulated in actinomycin D producing Streptomyces parvulus. Th eir relatively high intracellular concentrations during actinomycin D synthesis and identity of the time of onset of their synthesis with th at of actinomycin D synthesis leads us to suggest that they may functi on in the self-defense mechanism of actinomycin-producing organisms. H ere we present a combination of one-dimensional and two-dimensional H- 1- and C-13-NMR studies in solution and X-ray crystallography of THP(A ) and THP(B). Our results demonstrate identical conformations of THP(A ) and of THP(B) in H2O solution and in the crystal. THP(A) and THP(B) form zwitterionic molecules with the half-chair conformation. Both tec hniques, NMR and X-ray crystallography, indicate that the carboxyl gro up of THP(B) is in an axial position and that the carboxyl and the hyd roxyl groups of THP(A) are also in axial positions. The coplanar zigza g configurations (H-4 C4 C5 C6 H-6) of THP(A) and THP(B), deduced from NMR coupling measurements, were confirmed by X-ray diffraction studie s. The crystal structure of THP(B) indicates that the hydrogen atoms o f the methyl group are disordered, exhibiting two distinct conformatio ns, whereas the methyl group hydrogens of THP(A) exhibit only one conf ormation. This finding is in accordance with the dynamic properties of THP(A) and THP(B) derived from carbon spin-lattice relaxation rate me asurements. In spite of a different crystal packing and considerable d ifferences in the dynamic properties (T1) in solution, the two molecul es exhibit an almost identical conformation. The similar conformation of the two different crystals can be considered as evidence for a rela tively high internal stability of the molecule against intermolecular forces.