Amino Acids and Peptides. LI. Application of the 2-Adamantyloxycarbonyl (2-Adoc) Group to the Protection of the Hydroxyl Function of Tyrosine in Peptide Synthesis

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A 2-adamantyloxycarbonyl (2-Adoc) group was introduced as a protecting group for the hydroxyl function of tyrosine (Tyr) through the Shotten-Bauman reaction of 2-adamantyloxycarbonyl chloride with the copper complex of Tyr. The 2-Adoc group is stable to trifluoroacetic acid (TFA), 5.0 N HCl/dioxane, hydrogenation over a Pd catalyst and tertiary amine, and is easily removed by treatment with 1 M triflyoromethanesulfonic acid (TFMSA)-thioanisole/TFA and HF. Boc-Tyr(2-Adoc)-OH was prepared by the reaction of (Boc)₂O and H-Tyr(2-Adoc)-OH in the presence of triethylamine. Boc-Tyr(2-Adoc)-OH was successfully applied to the synthesis of Boc-Ala-Thr-Val-Lys(2-Adoc)-Phe-Lys(2-Adoc)-Tyr(2-Adoc)-Lys(2-Adoc)-Gly-OH, corresponding to the sequence 1-9 of Sulfolobus solfataricus RNase, and Boc-Tyr(2-Adoc)-Asp(O-2-Ada)-Gly(O-cHex)-Gly-OH, corresponding to the sequence 33-36 of S. solfataricus RNase.Boc-Phe-Lys(2-Adoc)-Tyr(2-Adoc)-Lys(2-Adoc)-Gly-OBzl was treated with anhydrous HF to afford H-Phe-Lys-Tyr-Lys-Gly-OH wighout any side reactions, in a good yield.