Abstract
The dipeptidic dihydroxyethylene isostere (27, 3R, 4R, 5S)-5-tert-butyloxy-carbonylamino-3,4-dihydroxy-2-isopropyl-3,4-O,O-isoprop-ylidene-6-cyclohexyl-hexanoic acid, 15, is a representative building block of an important class of unnatural dipeptide mimics. This pseudo-dipeptide of Cha-Val is considered to be a transition-state analog mimic that produces potent inhibitors of the enzyme renin when incorporated into angiotensinogen substrate peptide sequence (1). The same strategy has also been proven successful in the development of potent inhibitors of other aspartyl proteases, including HIV protease (2). This synthetic method has been proven successful in the preparation of 100-g-scale quantity of this important building block, which was used in the preparation of a potent HIV protease inhibitory peptidomimetic, PNU-75875, which was proven effective in the treatment of SIV-infected monkeys (3).
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References
Thaisrivongs, S., Pals, D. T., Kroll, L. T., Turner, S. R., and Han, F.-S. (1987) Renin inhibitors. Design of angiotensinogen transition-state analogues containing novel (2R,3R,4R,5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid. J. Med. Chem. 30, 976ā982.
Thaisrivongs, S., Tomasselli, A.G., Moon, J. B., Hui, J. O., McQuade, T. J., Turner, S. R., et al. (1991) Inhibitors of the protease from human immunodeficiency virus: design and modelling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective anti-viral activity. J. Med Chem. 34, 2344ā2356.
Martin, L. N., Soike, K. F., Murphey-Corb, M., Bohm, R. P., Roberts, E. D., Kakuk, T. J., et al. (1994) Effects of a peptidomimetic inhibitor of retroviral proteases (U-75875) on simian immunodeficiency virus infection in rhesus monkeys. Antimicrob. Agents Chemother. 38, 1277ā1283.
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Ā© 1999 Humana Press Inc., Totowa, NJ
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Scott, A., Conway, B.G., Krook, M.A. (1999). Synthesis of (2R, 3R, 4R, 5S)-5-tert-Butyloxycarbonylamino-3,4-Dihydroxy-2-1sopropyl-3,4-O,O-Isopropylidene-6-CyctohexyI-Hexanoic Acid. In: Kazmierski, W.M. (eds) Peptidomimetics Protocols. Methods in Molecular Medicineā¢, vol 23. Humana Press. https://doi.org/10.1385/0-89603-517-4:437
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DOI: https://doi.org/10.1385/0-89603-517-4:437
Publisher Name: Humana Press
Print ISBN: 978-0-89603-517-1
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