Urethane-protected amino acid-N-carboxyanhydrides
First Claim
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1. A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride having the structure:
- ##STR9## wherein R and R'"'"' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl and at least one of R and R'"'"' is other than hydrogen;
R" is alkyl, aryl, substituted alkyl or substituted aryl;
Z is oxygen or sulfur; and
n is 0, 1 or 2.
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Abstract
The invention relates to urethane-protected amino acid-N-carboxyanhydride and N-thiocarboxyanhydride compounds which are useful in peptide, polypeptide and protein synthesis. Disclosed herein is the preparation and use of these novel compounds.
81 Citations
72 Claims
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1. A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride having the structure:
- ##STR9## wherein R and R'"'"' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl and at least one of R and R'"'"' is other than hydrogen;
R" is alkyl, aryl, substituted alkyl or substituted aryl;
Z is oxygen or sulfur; and
n is 0, 1 or 2. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
- ##STR9## wherein R and R'"'"' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl and at least one of R and R'"'"' is other than hydrogen;
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34. N-9-fluorenylmethyloxycarbonyl-L-leucine-N-carboxyanhydride.
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35. N-9-fluorenylmethyloxycarbonyl-L-alanine-N-carboxyanhydride.
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36. N-α
- -(9-fluorenylmethyloxycarbonyl)-N-ε
-t-butyloxycarbonyl-L-lysine-N-carboxyanhydride.
- -(9-fluorenylmethyloxycarbonyl)-N-ε
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37. N-benzyloxycarbonyl-L-alanine-N-carboxyanhydride.
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38. N-benzyloxycarbonyl-L-leucine-N-carboxyanhydride.
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39. N-phenyloxycarbonyl-L-valine-N-carboxyanhydride.
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40. N-ethyloxycarbonyl-L-alanine-N-carboxyanhydride.
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41. N-benzyloxycarbonyl-L-phenylalanine-N-carboxyanhydride.
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42. N-phenyloxycarbonyl-L-alanine-N-thiocarboxyanhydride.
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43. N-(9-fluorenylmethyloxycarbonyl)-O-t-butyl-L-threonine-N-carboxyanhydride.
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44. N-9-fluorenylmethyloxycarbonyl-β
- -alanine-N-carboxyanhydride.
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45. N-t-butyloxycarbonyl-L-alanine-N-carboxyanhydride.
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46. N-(t-butyloxycarbonyl)-O-benzyl-L-serine-N-carboxyanhydride.
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47. N-phenyloxycarbonyl-1-amino-1-carboxy cyclohexane-N-carboxyanhydride.
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48. N-ethyloxylcarbonyl-α
- -aminoisobutyric acid-N-carboxyanhydride.
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49. A method for the synthesis of a polypeptide chain wherein an amino acid component is allowed to react with a second similar or dissimilar amino acid component and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure:
- ##STR10## wherein R and R'"'"' are hydrogen, alkyl, aryl, substituted alkyl, or substituted aryl and at least one of R and R'"'"' is other than hydrogen;
R" is alkyl, aryl, substituted alkyl or substituted aryl;
Z is oxygen or sulfur; and
n is 0, 1 or 2. - View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57, 58, 59)
- ##STR10## wherein R and R'"'"' are hydrogen, alkyl, aryl, substituted alkyl, or substituted aryl and at least one of R and R'"'"' is other than hydrogen;
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60. A method for the solid phase synthesis of a polypeptide chain on a soluble or insoluble support wherein a protected amino acid component is coupled by condensation reaction to the support containing substituent groups reactive with the carboxyl terminus end of said amino acid component. The coupled protected amino acid component is deprotected, neutralized if necessary, and a second similar or dissimilar protected amino acid component coupled to said deprotected amino acid compound, and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure:
- ##STR11## wherein R and R'"'"' are hydrogen, alkyl, cycloakyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl;
R" is alkyl, aryl, substituted alkyl or substituted aryl;
Z is oxygen or sulfur; and
n is 0, 1 or 2. - View Dependent Claims (61, 62, 63, 64, 65, 66, 67, 68, 69, 70)
- ##STR11## wherein R and R'"'"' are hydrogen, alkyl, cycloakyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl;
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71. A method of preparing urethane-protected amino acid N-carboxyanhydrides or N-thiocarboxyanhydrides having the structure:
- ##STR12## wherein R and R'"'"' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl;
R" is alkyl, aryl, substituted alkyl or substituted aryl;
Z is oxygen or sulfur; and
n is 0, 1 or 2, comprising reacting an amino acid N-carboxyanhydride or N-thiocarboxyanhydride having the structure;
##STR13## wherein R, R'"'"', Z and n are as designated above, with a haloformate having the structure;
##STR14## wherein X is halogen and R" is as designated above, in an inert diluent, under anhydrous conditions and in the presence of N-methylmorpholine. - View Dependent Claims (72)
- ##STR12## wherein R and R'"'"' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl;
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Current AssigneeBioresearch Incorporated
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Original AssigneeBioresearch Incorporated
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InventorsGoodman, Murray, Cohen, Michael P., Fuller, William D., Naider, Fred R.
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Primary Examiner(s)Moskowitz, Margaret
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Assistant Examiner(s)Perkins, Susan M.
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Application NumberUS07/168,087Time in Patent Office879 DaysField of Search530/335, 530/334, 530/337, 530/333, 548/227, 548/183, 544/97, 544/54, 540/488US Class Current530/335CPC Class CodesC07D 263/44 Two oxygen atomsC07D 277/34 Oxygen atomsC07K 1/023 using racemisation inhibiti...C07K 1/04 on carriers C07K1/003, C07K...
