Dicyclohexylcarbodiimide → SF 6,5

Participants

Reaction Steps

In Greenspoon et al., the design and preparation of nonpeptide analogues of RGD are described as follows. Compounds SF-6,5 and SFN-70 were prepared by coupling of methyl-5-aminovaleric acid with N-(butyloxycarbonyl)-6-aminohexanoic acid. The reaction was carried out using the 1,3-dicyclohexylcarbodiimide and 1 hydroxybenzotriazole in tetrahydroduran procedure. The butyloxycarbonyl protecting group was then removed by 50% trifluoroacetic acid in dichloromethane. Removal of the methyl ester protecting group was carried out with sodium hydroxide at pH 9.5, yielding SFN-70. The amine was converted to guanidium using 3,5-dimethylpyrazole-1-carboxamidine nitrate at pH 9.5 t produce the compound designated SF-6,5. Compound SF-6,6 was prepared from methyl-6-aminohexanoic acid and N-(butyloxycarbonyl)-6-aminohexanoic acid under the same conditions as used for SF-6,5. GK-5,5 was prepared from methyl-5-aminovaleric acid and N-(butyloxycarbonyl)-5-aminovaleric acid. Compounds AC-4 and AC-14 were prepared by stepwise synthesis either in solution or on a Merrifield resin, followed by deprotection and conversion of the amine to the guanidinium by the above-described methods. The final compounds were purified on preparative RP-18 columns and were judged pure by thin-layer chromatography (single spot) and 1H NMR spectroscopy. Compounds were characterized by 1H NMR and FAB-MS spectroscopy. The structures deduced from spectroscopy were consistent with the assigned structure. (Table 1). Table 1 shows a schematic presentation of the RGD-NH2 peptide and the corresponding non-peptide surrogates. Note that the distance between positions a and b is 11 atoms.

Provenance & Evidence