The conformation of new tetrahydropyrimidine derivatives in solution and in the crystal.
We have recently identified by NMR techniques two new tetrahydropyrimidine derivatives, 2-methyl-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. Their relatively high intracellular concentrations during actinomycin D synthesis and identity of the time of onset of their synthesis with that of actinomycin D synthesis leads us to suggest that they may function in the self-defense mechanism of actinomycin-producing organisms. Here we present a combination of one-dimensional and two-dimensional 1H- and 13C-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 techniques, NMR and X-ray crystallography, indicate that the carboxyl group of THP(B) is in an axial position and that the carboxyl and the hydroxyl groups of THP(A) are also in axial positions. The coplanar zigzag configurations (H4 C4 C5 C6 H6) of THP(A) and THP(B), deduced from NMR coupling measurements, were confirmed by X-ray diffraction studies. The crystal structure of THP(B) indicates that the hydrogen atoms of the methyl group are disordered, exhibiting two distinct conformations, whereas the methyl group hydrogens of THP(A) exhibit only one conformation. This finding is in accordance with the dynamic properties of THP(A) and THP(B) derived from carbon spin-lattice relaxation rate measurements. In spite of a different crystal packing and considerable differences in the dynamic properties (T1) in solution, the two molecules exhibit an almost identical conformation. The similar conformation of the two different crystals can be considered as evidence for a relatively high internal stability of the molecule against intermolecular forces.
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Organic Chemistry Department, Weizmann Institute of Science, Rehovot, Israel.
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Lapidot
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D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry*; D014961:X-Ray Diffraction
D011743:Pyrimidines; D012996:Solutions; C081912:2-methyl-4-carboxy-5-hydroxy-3,4,5,6-tetrahydropyrimidine; C081913:2-methyl-4-carboxy-3,4,5,6-tetrahydropyrimidine