Reaktion #701951

Reaktionsgleichung

t-butyloxycarbonyl-L-isoleucine

t-butyloxycarbonylvaline

t-butyloxycarbonyl-L-isoleucine

t-butyloxycarbonylisoleucine

t-butyloxycarbonyl-threonine

t-butyloxycarbonyl-L-valine

→

t-butyloxycarbonyl-threonylvalylisoleucine

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe resin is then washed as usual
2. 2
   Sonstigeto remove by-products and completeness of the reaction
3. 3
   Sonstigeis checked by the Kaiser color reaction

Vorschrift

A solution of 5.3 grams of t-butyloxycarbonyl-L-isoleucine (21.2 mmole), 2.5 milliliters of triethylamine (18 mmole) in a 2-methyltetrahydrofuran solvent is prepared and 20 grams of Merrifield resin is added thereto. Prior to use, the resin is washed with methanol, distilled water, ethanol, and methylene chloride and then dried in vacuo at 100° C. Prior to use, the 2-methyltetrahydrofuran is distilled over a sodium dispersion, and the triethylamine is distilled over phenylisocyanate and then redistilled over a sodium dispersion. The mixture is refluxed for approximately 72 hours to effect esterification of the blocked amino acids to the resin. After the esterification reaction, the resin is washed with tetrahydrofuran, ethanol, glacial acetic acid, ethanol, distilled water, ethanol, and methylene chloride, and then dried in vacuo at 100° C. for three hours. Approximately 21.5-22 grams of t-butyloxycarbonyl-L-isoleucine resin ester is obtained. This coupling of the t-butyloxycarbonylvaline to the t-butyloxycarbonylisoleucine resin ester is performed in essentially the same manner as the coupling of t-butyloxycarbonyl-L-valine to the t-butyloxycarbonyl-L-isoleucine resin ester disclosed in Example 8. However, because of the even greater steric hindrance, the reaction is allowed to proceed for 24 hours. The resin is then washed as usual to remove by-products and completeness of the reaction is checked by the Kaiser color reaction. The addition to t-butyloxycarbonyl-threonine to obtain t-butyloxycarbonyl-threonylvalylisoleucine resin ester, the cleavage of the peptide from the resin to obtain t-butyloxycarbonyl-threonylvalylisoleucine, and its subsequent isolation and purification are performed in essentially the same manner as in the preparation of threonylvalylleucine disclosed in Example 8. The tripeptide, threonylvalylisoleucine, is obtained in an amount of about 600 milligrams (68% yield).

Quelle