184684-99-9

Upstream product

• 100-51-6 benzyl alcohol 
• 3401-36-3 (N-benzyloxycarbonyl)-L-alanine N-hydroxysuccinimide ester 
• 184684-98-8 (S)-2-Amino-3-{4-[bis-(2-hydroxy-ethyl)-amino]-phenyl}-propionic acid benzyl ester 
• 949-99-5 4-nitro-3-phenyl-L-alanine 
• 184684-97-7 N-tert-butyloxycarbonyl-p-bis(2-hydroxyethyl)amino-L-phenylalanine benzyl ester 
• 184684-96-6 p-amino-N-tert-butyloxycarbonyl-L-phenylalanine benzyl ester 
• 127977-25-7 benzyl 2(S)-<(tert-butoxycarbonyl)amino>-3-(4'-nitrophenyl)propionate 

Downstream Products

• 184685-02-7 N-(N-benzyloxycarbonyl-L-alanyl)-p-bis(2-chloroethyl)amino-L-phenylalanine benzyl ester 

Relevant academic research and scientific papers

Synthesis of α-aminoacyl derivatives of melphalan for use in antibody directed enzyme pro-drug therapy

L-Alanyl-, D-alanyl-, L-prolyl-, L-pyroglutamyl- and D- phenylalanylmelphalan were synthesized in 8 steps, with the reactive nitrogen mustard moiety formed at the penultimate step. After protection of p- nitrophenylalanine with benzyl ester and N-t-butyloxycarbonyl (BOC) groups, the aromatic nitro was reduced to an amine which was reacted with ethylene oxide to give a product with a bis(2-hydroxyethyl)amino moiety. After removal of BOC, it was coupled to the relevant N-benzyloxycarbonyl-α-amino acid. Chlorination of hydroxyethyl yielded the bis(2-chlorethyl)amino compound. Final removal of protecting groups was by catalytic hydrogenolysis.

Synthesis of N-α-aminoacyl derivatives of melphalan for potential use in drug targeting

N-L- and D-alanyl derivatives (9a, 9b) of melphalan (1) have been synthesized in eight steps (9a, 22%; 9b, 18% overall yield) from p-nitro-L-phenylalanine.