Synthesis and application in SPPS of a stable amino acid isostere of palmitoyl cysteine

(S)-2-Amino-4-(2-pentadecyl-1,3-dioxolan-2-yl)-butanoic acid, 11, Pdiob, a synthetic analogue C-isostere of palmitoylated cysteine, has been prepared starting from tetrabenzyl glutamic acid. The less hindered benzyl carboxylate ester was transformed into the corresponding β-ketophosphonate and subjected to a Horner-Wadsworth-Emmons reaction followed by hydrogenation/hydrogenolysis. This product was used for the preparation on solid phase and under microwave dielectric heating of a highly lipidated peptide that can be considered as an acid stable analogue of the C-terminus of the H-Ras heptapeptides 180-186. © 2008 Elsevier Ltd. All rights reserved

Solid-Phase Synthesis of Conformationally Constrained Peptidomimetics Based on a 3,6-Disubstituted-1,4-diazepan-2,5-dione Core

Starting from a chlorotrityl resin-linked hydroxylamine, a hydroxamic dipeptide having serine at the N-terminus was prepd. by using DMTMM [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] as the coupling agent.  Under microwave heating, Mitsunobu cyclization of the hydroxamic dipeptide gave a 3,6-disubstituted-perhydro-diazepin-2,5-dione in very good yields.  Thus, by using Fmoc-Ser-Glu(OCH2CH:CH2)-NH-O-Resin, H3CCO-Gly-OH and H-Pro-OMe, peptidomimetic I was prepd. in four steps in 75% yield

Solution structure of folic acid. Molecular Mechanics and NMR investigation

he structure of folic acid in solution was investigated by nuclear magnetic resonance (NMR) and theoretical calculations. Dynamical information and geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear NOESY spectra and hetero-nuclear 1H–13C NOE experiments. This set of experimental data was used for the molecular mechanics and molecular dynamic calculations. The accuracy of the final structure was established by the RNMR factor, which was calculated comparing the experimental NOESY cross-peaks intensities and the corresponding values simulated by using the complete relaxation matrix analysis (CORMA) approac