Divergent Synthesis, Antiproliferative and Antimicrobial Studies of 1,3-Aminoalcohol and 3-Amino-1,2-Diol Based Diaminopyrimidines.

A series of novel diaminopyrimidines containing pinane moieties were synthesized via an efficient methodology starting from pinane-based aminoalcohols, aminodiols and 2,4-dichloropyrimidines. Bioassay tests demonstrated that compound 18a displayed much stronger antiproliferative activities against four human cancer cell lines (HeLa, Siha, MDA-MB-231, MCF-7 and A2780) than positive control cisplatin. In particular, compound 22a was found to be selective in inhibiting HeLa cell proliferation with cancer cell growth inhibition values higher than 95 %. Moreover, the in vitro screening of prepared compounds against different bacterial and fungal strains is reported. The results revealed that 12b and 17a, the most promising compounds, displayed selective inhibition for the Gram-positive bacteria (B. subtilis and S. aureus) with percent inhibition values ranging from 75 to 95 % at 10 µg/mL concentration. Both selective inhibition and the in vitro activity values demonstrated that these compounds have the potential to be developed into clinically important therapeutic choices for the treatment of infections caused by B. subtilis and S. aureus.

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols.

A library of pinane-based 2-amino-1,3-diols was synthesised in a stereoselective manner. Isopinocarveol prepared from (-)-α-pinene was converted into condensed oxazolidin-2-one in two steps by carbamate formation followed by a stereoselective aminohydroxylation process. The relative stereochemistry of the pinane-fused oxazolidin-2-one was determined by 2D NMR and X-ray spectroscopic techniques. The regioisomeric spiro-oxazolidin-2-one was prepared in a similar way starting from the commercially available (1R)-(-)-myrtenol (10). The reduction or alkaline hydrolysis of the oxazolidines, followed by reductive alkylation resulted in primary and secondary 2-amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring-ring tautomerism was observed in CDCl3.