558 MEDICINAL CHEMISTRY
Figure 9.2 Synthesis of Peramivir. The starting material, (−)-lactam, 1 , underwent hydroly-
sis with methanol in acidic conditions. The amino group of the resulting amino ester was pro-
tected with a t-butyloxycarbonyl group (Boc) to give 2. A [3+2] cycloaddition between 2 and
the nitrille oxide produced from 2-ethyl-l-nitrobutane, phenyl isocyanate, and triethylamine
gave 3 and a mixture of isomers. Compound 3 was isolated, then hydrogenated in a 1:1
methanol:HCl (aq.) mixture in the presence of PtO 2 at 100 psi to give an amine hydrochloride.
This was then reacted with acetic anhydride to give the corresponding N-acetyl derivative
4. Subsequent to this, the amine was deprotected in an ether–acid solution to give 5. Compound
5 was guanylated with pyrazole carboxamidine hydrochloride in DMF in the presence of
diisopropylethylamine. Finally, treatment with NaOH gave the desired compound, Peramivir.
(Reference: Y. S. Babu, P. Chand, S. Bantia, P. Kotian, A. Dehghani, Y. El-Kattan, T. -H. Lin,
T. L. Hutchinson, A. J. Elliot, C. D. Parker, S. L. Ananth, L. L. Horn, G. W. Laver, J. A.
Montgomery, (2000). J. Med. Chem. 43: 3482.)