The deprotection of the Boc-amino group of the aspartic acid of (X) allows its condensation with the protected S-(tetra-O-acetyl-beta-D-galactopyranosyl)-L-cysteine (XI) affording the monocyclic hexapeptide (XII), which is treated first with HF, SMe2, p-cresol, and p-thiocresol to eliminate the solid phase resin and the Boc protecting group of the cysteine residue, and then cyclized by means of PyBop to afford the bicyclic hexapeptide (XIII). Finally, this compound is treated with sodium methoxide (c>5 mM) for more than 5 h. to give a mixture of the already known galactopyranosyl-hexapaptide Neuronorm (XIV) and the target compound (the dehydroalanyl derivative), which were separated by RP-HPLC.
The solid phase method for the synthesis of peptides is here used starting with a phenylacetamidomethyl resin coupled with boc-protected-L-leucine (I), which was coupled successively with protected L-2,3-diaminopropionic acid (II) yielding dipeptide (III), with protected L-phenylalanine (IV), yielding tripeptide (V), with protected L-tryptophan (VI) yielding tetrapeptide (VII), and with protected L-aspartic acid (VIII), yielding pentapeptide (IX). The cyclization of (IX) by selective deprotection of the side chains of diaminopropionic acid and aspartic acid with piperidine in DMF, followed by cyclization by means of PyBop and DIEA in DMF affords the cyclic pentapeptide (X).