Phosphorus–Nitrogen Compounds. Part 24. Syntheses, Crystal Structures, Spectroscopic and Stereogenic Properties, Biological Activities, and DNA Interactions of Novel Spiro-ansa-spiro- and Ansa-spiro-ansa-cyclotetraphosphazenes

The reactions of octachlorocyclotetraphosphazene,
N4P4Cl8, with N2O2 donor-type
aminopodands (1a, 1b, 1g, and 1h) afforded two kinds of derivatives, namely, spiro-ansa-spiro
(sas) (2a, 2b, 2g, and 2h) and ansa-spiro-ansa (asa) (3a and 3b) phosphazenes. The partly substituted sas phosphazenes (2a and 2b) reacted
with excess pyrrolidine and morpholine in tetrahydrofuran to produce
the tetrapyrrolidino (2c and 2d) and morpholino
(2e and 2f) derivatives. The reactions of
the asa phosphazenes (3a and 3b) with excess pyrrolidine and morpholine produced gem-2-trans-6-dichloropyrrolidinophosphazenes (3c and 3d) and -morpholinophosphazenes (3e and 3f). However, the fully substituted products
were not obtained in these solvents. In addition, the expected fully
substituted compound was not obtained from the reaction of 3a with excess pyrrolidine by standard or microwave-assisted methods.
The reaction of the long-chain starting compound (1g)
with N4P4Cl8 gave sas (2g) and the interesting 2,6-ansa-spiro-bicyclo product
(bicyclo-2,6-as; 4g), while the reaction
of 1h with N4P4Cl8 yielded
only sas (2h). The structural investigations
of the compounds were verified by elemental analyses, mass spectrometry,
Fourier transform infrared, and DEPT, HSQC, HMBC, 1H, 13C, and 31P NMR techniques. The crystal structures
of 2b, 3a, 3b, 3e, and 4g were determined by X-ray crystallography. Compounds 2a–2h, 3a–3f, and 4g had two stereogenic P atoms. Compound 3b had one enantiomer according to the Flack parameter, and 3f was a racemic mixture, as shown by chiral high-performance
liquid chromatography and chiral-solvating-agent, (R)-(+)-2,2,2-trifluoro-1-(9′-anthryl)­ethanol, experiments.
Furthermore, compounds 2a, 2c, and 2d exhibited weak antibacterial activity against (G+) bacterium,
and 3c and 3d displayed moderate antifungal
activity against Candida tropicalis. Gel electrophoresis
data demonstrated that 2e, 3c, and 3e promoted the formation of DNA cleavage. The prevention
of BamHI digestion by 2a–2f and 3a–3f, except 2b and 2e, disclosed binding with GG nucleotides
in DNA.