Maria J. Lyapova

β-Ureido acids and dihydrouracils—VII: Applications of proton resonance spectroscopy—XXXII nmr spectra and conformation of dihydrouracils and related compounds

Abstract The NMR spectia of the cis and trans -isomers of 5,6-tetramethylenedihydrouracil (2,4-dioxo-decahydroquinazoline, TMDHU), 5,6-dimethyldihydrouracil (DMeDHU), 5,6-diphenyldihydrouracil (DPhDHU), 5-methyldihydroorotic acid (MeDHO), as well as those of dihydroorotic acid (DHO) and its methyl ester, and 6-phenyldihydrouracil (PhDHU) are reported. The J trans and J 16 coupling constants of these and other dihydrouracils are used in the conformational analysis. Contrary to earlier suggestions 3,4 of widely varying distortion of the dihydrouracil ring, the variation of cis J 56 and J 16 is best explained by electronegativity and equilibrium effects. Carboxy and methoxycarbonyl groups at C-6 prefer the axial orientation. A phenyl group at C-6. and the two phenyls in trans -DPhDHU, are predominantly axial in dimethyl sulphoxide, but equatorial in trifluoroacetic acid. The coupling constants of the cis and trans isomers of 2-ureidocyclohexane carboxylic (UCHA) and of the erytho and threo isomers of 2-methyl-3-ureidobutyric acid (MeUBA) and of 2,3-diphenyl-3-ureidopropionic acid (DPhUPA) indicate that with both isomers of MeUBA conformers with gauche hydrogens are preferred, while in the case of DPhUPA trans hydrogens predominate.

NMR SPECTRA AND STEREOCHEMISTRY OF DIASTEREOISOMERIC 4,5-DIPHENYL-CYCLOPHOSPHAMIDES

Abstract The conformational distribution and relative configuration of four diastereoisomeric pairs of 4,5-diphenyl-cyclophosphamides and their N-methyl analogues were determined by means of 1H, 13C, 31P NMR and IR spectroscopy.

CONFORMATIONS OF 4,5,6-TRIPHENYL-TETRAHYDRO-1,3-THIAZINE-2-THIONES AND THEIR N-ALKYL DERIVATIVES. UNUSUAL THIAZINETHIONE OR AZETIDINE FORMATION UPON REACTION OF 3-AMINO- AND 3-METHYLAMINO-1,2,3-TRIPHENYLPROPYL CHLORIDES WITH POTASSIUM ETHYLXANTHATE

Abstract Reaction of 3-amino- or 3-methylamino-1,2,3-triphenylpropyl chlorides (6 or 7) with potassium ethylxanthate leads to 4.5.6-triphenyl-tetrahydro-,3-thiazine-2-thione 1 or 1-methyl-2,3,4-triphenylazetidine 8 depending on the N-substitution. Conformational distribution of all possible diastereoisomeric thiazinethiones 1 and their N-alkyl derivatives 2–5 is determined by means of 1H NMR spectroscopy. Allylic strain caused by N- substituents in the trans,cis-isomers strongly shifts the equilibrium between conformations with a,a,e or e,e,a phenyl groups towards the conformer with an axial neighbouring Ph-4 group. Vicinal couplings data for the diastereoisomeric azetidine 8 show different ring geometry depending on the configuration.

Synthesis of a series of vicinal diamines with potential biological activity

A broad range of vicinal diamines based on styrene oxide are synthesisedvia mixtures of regioisomeric amino alcohols. The ring opening of the intermediate aziridinium ions by primary amines proceeds with high regioselectivity, leading to the target diamines as single regioisomers for all reaction series. The compounds are of potential biological interest as ligands for cisplatin analogues. Anticancer activity tests of both groups of compounds are in progress.

Unusual Azetidine or Oxazine Formation upon Reaction of O-Ethyl Dithiocarbonate with 1,2,3-Triphenyl-3-Phthalimidopropyl Iodides; Erythro Selectivity in the Reaction of Iodotrimethylsilane with Phthalimidopropanols

Reaction of isomeric 1,2,3-triphenyl-3-phthalimidopropanols with hexamethyldisilane and iodine gave highly selectively iodides 3 with 1,2-erythro configuration which treated with O-ethyl dithiocarbonate yielded from ET-3 the xanthate ester 4, the trans,trans-dihydrooxazine 5 and the olefin 6 as major products while from EE-3 the cis,trans-azetidine 7 was obtained in 75% yield.

SYNTHESIS AND ANTICANCER SCREENING OF DIASTEREOISOMERIC 4,5-DIPHENYL- AND 3-METHYL-4,5-DIPHENYLCYCLOPHOSPHAMIDES

Abstract The four possible diastereoisomers of 4,5-diphenylcyclophosphamides (2–5) and their N-methyl analogues (6–9) have been synthesized via condensation of aminopropanols 10 and 11 (threo- and erythro) with bis-(2-chloroethyl)-phosphoramidic dichloride 12. Anticancer screening tests against L 1210 lymphoid leukaemia in mice did not show any therapeutic activity.