A FACILE METHOD FOR THE SIDE-CHAIN PROTECTION OF ALPHA-METHYL-BETA-3,4-DIHYDROXYPHENYL-L-ALANINE (ALPHA-MEDOPA) FOR SOLID-PHASE PEPTIDE-SYNTHESIS

Hsieh, KH; Demaine, MM

HERO ID

1198779

Reference Type

Journal Article

Year

1991

HERO ID 1198779
In Press No
Year 1991
Title A FACILE METHOD FOR THE SIDE-CHAIN PROTECTION OF ALPHA-METHYL-BETA-3,4-DIHYDROXYPHENYL-L-ALANINE (ALPHA-MEDOPA) FOR SOLID-PHASE PEPTIDE-SYNTHESIS
Authors Hsieh, KH; Demaine, MM
Journal Synthesis
Issue 1
Page Numbers 59-62
Abstract Two approaches have been used to prepare N-alpha-tert-butoxycarbonyl-alpha-methy-beta-3,4-dimethoxy-, or dibenzyloxyphenyl-L-alanine, N-alpha-Boc-alpha-MeDopa (R)2, where R is the methyl or benzyl ether. In the first approach, alpha-methyl-beta-3,4-dihydroxyphenyl-L-alanine (alpha-MeDopa) is reacted with di-tert-butyl dicarbonate (Boc2O) in the presence of sodium bicarbonate under anhydrous conditions. The resultant N-protected derivative (Boc-alpha-MeDopa) is methylated with methyl iodide/sodium carbonate, followed by reaction with methyl iodide/tetramethylammonium hydroxide, and saponification with potassium hydroxide in aqueous dioxane to give N-alpha-tert-butoxycarbonyl-alpha-methyl-beta-3,4-dimethoxyphenyl-L-alanine, Boc-alpha-MeDopa(Me)2, in 30 % overall yield. In the second approach, methyl ester of alpha-methyl-beta-3,4-dihydroxyphenyl-L-alanine is prepared by the thionyl chloride/methanol procedure, followed by N-protection with di-tert-butyl dicarbonate/sodium bicarbonate, sidechain protection with benzyl chloride/tetramethylammonium hydroxide, and saponification with sodium hydroxide in aqueous dioxane to give N-alpha-tert-butoxycarbonly-alpha-methyl-beta-3,4-dibenzyloxyphenyl-L-alanine, Boc-alpha-MeDopa(CH2Ph)2, in 46 % overall yield. The latter derivative has been incorporated into angiotensin II under stepwise solid-phase peptide synthesis and solution coupling conditions.<
Wosid WOS:A1991EU00700017
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science A1991EU00700017 Journal:SYNTHESIS-STUTTGART
Is Public Yes
Is Qa No