Novel class of silicon-based protective groups for the side chain of tyrosine.
A novel class of silyl-based protective groups compatible with the Bpoc/t-Bu strategy has been developed for the side chain of tyrosine. Carbobenzyloxy (CBZ) and biphenylisopropyloxy (Bpoc)-O-beta-trimethylsilylethyl-tyrosine (10 and 12) and CBZ-O-beta-dimethylphenylsilylethyl-tyrosine 14 were prepared in reasonable yields and in very high purity. The trimethylsilylethyl (TMSE) group proved to be 3-4 times more stable than the tert-butyl ether group towards 0.5% TFA. The latter is removed up to 4% during the acidolysis of the Bpoc group. As expected, the dimethylphenylsilylethyl (DMPSE) group was even more resistant towards 0.5% TFA (five time greater than the TMSE analog). Both silyl protective groups were found to be resistant towards a variety of reagents used in peptide synthesis, such as trialkylamines, hydroxybenzotriazole, trialkylphosphine and nucleophiles. They are readily removed in neat TFA in 5-20 min in the absence of cation scavengers, without any detectable alkylation of the phenolic ring. The application of the new silyl-based protective group was demonstrated by the synthesis of the C-terminal 29 amino acid peptide of the basic pancreatic trypsin inhibitor by the prior thiol capture methodology. The protected octapeptide BocC(Acm)QT)(tBu)FVY(TMSE)GG-PO-dibenzofuranthiol++ + was synthesized by solid-phase peptide synthesis using Bpoc-(O-TMSE)-Tyr-OH in greater than 90% yield and coupled to an unprotected 21-mer. The partially blocked, purified peptide was deprotected quantitatively in neat TFA in 1 h.
Fotouhi
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N
Massachusetts Institute of Technology, Cambridge.
Kemp
D S
DS
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012825:Silicon / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014443:Tyrosine / Q000138:chemical synthesis* / Q000737:chemistry
D010455:Peptides; D013438:Sulfhydryl Compounds; D014443:Tyrosine; D012825:Silicon