CATALYTIC HYDROGENOLYSIS IN LIQUID AMMONIA.* CLEAVAGE OF Nα‐BENZYLOXYCARBONYL GROUPS FROM CYSTEINE‐CONTAINING PEPTIDES WITH tert‐BUTYL SIDE CHAIN PROTECTION
- 1 May 1978
- journal article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 11 (5) , 329-339
- https://doi.org/10.1111/j.1399-3011.1978.tb02857.x
Abstract
To exemplify the extension to synthesis of sulfur‐containing peptides of the Nα‐benzyloxycarbonyl and side chain tert‐butyl protective group combination, somatostatin has been synthesized via incremental chain elongation starting from the COOH‐terminal cysteine. Cleavage of the Nα‐benzyloxycarbonyl groups was achieved in high yield, at each stage, by palladium‐catalyzed hydrogenation in liquid ammonia. All side chain functionalities including the cysteine thiol groups were blocked by tert‐butyl‐derived groups. Each gave rise to individual n.m.r. signals which permitted sensitive characterization of all intermediate protected peptides. Mild conditions were used for the removal of all protecting groups from the completed somatostatin tetradecapeptide. The tert‐butyl thiol protective groups were readily and completely cleaved by mercuric acetate at pH 4. Oxidation of dihydrosomatostatin with potassium ferricyanide provided somatostatin in good yield. The results indicate that the absolute selectivity between α‐amine and side chain protective group cleavage afforded by Nα‐benzyloxycarbonyl hydrogenolysis in the presence of ‐tert‐butyl groups may now be extended to synthesis of cysteine‐ and methionine‐containing peptides.Keywords
This publication has 32 references indexed in Scilit:
- Studies on peptides. LII. Application of the trifluoromethanesulphonic acid procedure to the synthesis of a peptide with somatostatin activity.CHEMICAL & PHARMACEUTICAL BULLETIN, 1975
- Solid phase synthesis of growth hormone-release inhibiting factorBiochemical and Biophysical Research Communications, 1973
- Synthesis of a peptide with full somatostatin activityBiochemical and Biophysical Research Communications, 1973
- Total synthesis of hypothalamic “somatostatin”Biochemical and Biophysical Research Communications, 1973
- Reinvestigation of the mixed carbonic anhydride method of peptide synthesisJournal of the American Chemical Society, 1967
- The Tertiary Butyl Group as a Blocking Agent for Hydroxyl, Sulfhydryl and Amido Functions in Peptide SynthesisJournal of the American Chemical Society, 1963
- A Method of Synthesis of Long Peptide Chains Using a Synthesis of Oxytocin as an ExampleJournal of the American Chemical Society, 1959
- The Preparation of Peptides Using Mixed Carbonic—Carboxylic Acid AnhydridesJournal of the American Chemical Society, 1952
- Über die Abhängigkeit der katalytischen Hydrierung von der Gegenwart des SauerstoffsBerichte der deutschen chemischen Gesellschaft (A and B Series), 1921
- Über Hydrierung und DehydrierungEuropean Journal of Inorganic Chemistry, 1912