Search

A cyclic pseudopeptide containing the RGD sequence has been synthesized in high yield by ring-closing metathesis using a Grubbs’ catalyst in tetrahydrofuran. Conformational analysis has been correlated to structure modeling and preliminary biological activity as an integrin binding inhibitor has been evaluated.

Ring closing metathesis has been performed for the first time on a soluble poly(ethylene glycol) supported substrate in the presence of Grubbs' catalyst and provided in good yields 6-, 7- and 8-membered ring aminoacid derivatives. The presence of the polymer required the use of a higher amount of ruthenium complex but the addition of a cofactor such as 1-octene improved the turnover of the catalyst. On the other hand, a Schiff base protected glycine supported on a poly(ethylene glycol) reacted readily with various electrophiles in the presence of an inorganic base under microwave activation.

A new soluble poly(ethylene glycol)-supported protecting group of the SES (silylethylsulfonyl) type has been prepared and utilized in the synthesis of cyclic amino esters by ring-closing metathesis (RCM). Acidic cleavage from the support was performed to recover the fully deprotected amino acids. More conventional deprotection conditions with fluoride anions resulted in aromatization of the heterocycles in the case of the 6-membered ring and provided a new route to the synthesis of substituted pyridines. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).

Poly(ethyleneglycol) (PEG) substituted by various organic moities were analyzed by electrospray ionization (ESI) mass spectrometry in order to determine the best experimental protocol allowing reproducible, sensitive and informative spectra in the search of completely automated high throughput identification of libraries generated by the liquid-phase methodology. The nature of the eluent and of the PEG derivatization as well as the value of the sampling cone voltage were investigated by comparing the recorded oligomer distributions.

Syntheses carried out on soluble polymers, such as polyethylene glycol (PEG), benefit the advantages of both solution-phase and solid-phase syntheses. The choice of the reaction solvent governs the polymer solubility. Synthetic steps are conducted under homogeneous conditions whereas purifications are performed by filtration after polymer precipitation. This alternative strategy, known as liquid-phase chemistry, has been investigated to prepare combinatorial libraries.The fact that soluble polymer supported molecules are directly amenable to standard spectroscopic methods, including NMR (1H, 13C) and ESI or MALDI mass spectrometry (ElectroSpray and Matrix Assisted Laser Desorption Ionization) allows to perform to in situ reaction monitoring without the need to release the compound from the polymeric support.We report a general methodology to characterize step by step soluble polymer supported organic molecules by MALDI and ESI mass spectrometry. High throughput analyses were targeted to fullfil combinatorial chemistry requirements. Data acquisition and interpretation were automated through the design of specific experimental protocols and a data managment software. MALDI mass spectrometry was appropriate to analyze pure supported molecules whereas ESI mass spectrometry coupled to liquid chromatography was required to unravel PEG mixtures.