Table 3. Syntheses of Peptide Drugs Using Piperidine and Dipropylamine as Fmoc Removal Agents.

Cpd. sequencea	Fmoc deprotection reagentb	temperature (°C)	crude yieldc(%)	crude purityd (%)	isolated yielde (%)
Afamelanotide	20% PPR	60	70	46	17
Ac-SYSNleEHfRWGKPV	25% DPA	60	45	50	10
Bivalirudin	20% PPR	60	n.d.	77	46
fPRPGGGGNGDFEEIPEEYL-OH	25% DPA	60	n.d.	77	39
	20% PPR	90	6.6	28	n.d.
	25% DPA	90	4.6	25	n.d.

^aOne-letter code for amino acids, D-amino acids in lower case. C-terminus is carboxamide for Afamelanotide and carboxyl for Bivalirudin. Ac, acetyl group; Nle, norleucine.

^bPPR, piperidine; DPA, dipropylamine. Percentages (%) are in v/v.

^cCrude yield is calculated as explained in Table 1.

^dThe crude product after resin cleavage was precipitated, washed, dried, lyophilized and analyzed by analytical HPLC to determine the percentage of desired product and other byproducts.

^eIsolated yields were calculated after preparative RP-HPLC purification according to the amount of resin and its indicated loading. n.d., not determined.