الفهرس | Only 14 pages are availabe for public view |
Abstract Several years ago Einhorn and his coworkers introduced the reaction of ’Boc-Ncprotected iminodiacetic acid diesters with various electrophiles to give the symmetrically disubstituted compounds. Later Boger et al described a simple, versatile, and general approach to solution phase syntheses according to the combinatorial approach. This approach was illustrated employing the synthesis of IDA diamide libraries with a 2-fold dimerization to convert the monomers first to dimers and then to tetramers. More recently, liquid phase methods have been developed to provide a novel series of iminodiacetic acid derivatives targeting the integrin receptors. It seemed of interest to study the behavior of N-protected iminodiacetic acid during the preactivation step and the coupling with different amino acid derivatives according to the methods of solution and solid phase synthesis. For this reason N-protected iminodiacetic acids (Z-IDA 161, Boc- IDA 148, Fmoc-IDA 162 and Bsmoc-IDA 163) have been synthesized by two techniques: a) via chloroformate derivatives or b) via the Bolin technique. Appropriate materials were identified by IR, IH-NMR and elemental analysis. Also several coupling reagents were examined. These included TCFH 158, TFFH 159, HA TU 139, HBTU 118 and HSTU 160, which were synthesized from tetramethylurea with POCl3 to yield first the dichloro salt. Subsequently by anion exchange TCFH was obtained and subsequent treatment of this compound with KF at 60°C or HOBt, HOAt or KOSu at 0 °C gave the desired coupling reagents TFFH 159, HBTU 118, HATU 139 or HSTU 160 respectively. |