The Practice of Peptide Synthesis

During the years 1980-81, as guests of the Deutsches Wollforschungsinstitut in Aachen, Germany, we were working on a small book entitled, "Principles of Peptide Synthesis". In the library of the Institute we noted that the volumes of Houben-Weyl's Handbuch der Organischen Chemie dealing with peptide synthesis were so much in use that they were ready to fall apart because the researchers of the Institute consulted them with amazing regularity. They were looking for references, but even more for experimental details which could be adapted to the particular problem they happened to face. In planning a new synthetic endeavor they tried to lean on the experience of others in analogous situations. This suggested to us that a smaller and hence more tractable book may be needed, a volume which can be kept on or near the bench to make examples of fundamental methods readily available in the laboratory. Such a collection could save numerous short trips to the library, a point particularly important where a library well equipped with the sources of the literature of peptide synthesis is not near at hand. Also, we thought that the envisaged book may be welcome by those who are more versed in English than in German. To the best of our knowledge no similar publication is available.

InhaltsangabeI Introduction.- II Protecting Groups.- 1 Introduction of Amine Protecting Groups.- 1.1 The p-Toluenesulfonyl Group.- p-Toluenesulfonyl-l-isoleucine.- 1.2 Phthalyl (Phthaloyl, Pht) Amino Acids.- Phthalyl-l-leucine.- 1.3 The Benzyloxycarbonyl Group.- Benzyloxycarbonyl-l-proline.- Benzyloxycarbonyl-l-leucine.- N?-Benzyloxycarbonyl-l-arginine 12.- Benzyloxycarbonyl-l-aspartic Acid ?-Benzyl Ester.- 1.4 4-Methoxybenzyloxycarbonylamino Acids.- 1.5 The tert-Butyloxycarbonyl (Boc) Group.- 1.5.1 Introduction of the tert-Butyloxycarbonyl Group with 2-tert-Butyloxycarbonyloximino-2-phenylacetonitrile.- tert-Butyloxycarbonyl-glycine.- tert-Butyloxycarbonyl-l-tryptophan.- 1.5.2 Introduction of the tert-Butyloxycarbonyl Group with tert-Butyl Pyrocarbonate.- 1.6 The Biphenylylisopropyloxycarbonyl (Bpoc) Group.- Bpoc-l-leucine.- Bpoc-l-leucine.- 1.7 The 9-Fluorenylmethyloxycarbonyl (Fmoc) Group.- 9-Fluorenylmethyl Chlorocarbonate.- 9-Fluorenylmethyloxycarbonyl-l-tryptophan.- 1.8 o-Nitrophenylsulfenylamino Acids.- 1.9 2-Trimethylsilylethyloxycarbonylamino Acids.- 4-Nitropheny1-2-Trimethylsilylethyl Carbonate.- 2-Trimethylsilylethyloxycarbonyl-l-proline.- 1.10 Maleoylamino Acids and Maleoyl-Peptides.- N-Methoxycarbonylmaleimide.- Maleoyl-glycine.- Maleoyl Peptides.- 1.11 Triphenylmethyl-amino Acids.- Trityl-l-leucine.- N-Trityl Amino Acids.- 2 Blocking of the ?-Carboxyl Group.- 2.1 Methyl Esters.- 2.2 Ethyl Esters.- 2.2.1 Esterification with the Help of Gaseous HCl.- l-Tyrosine Ethyl Ester.- 2.2.2 Esterification Catalyzed by p-Toluenesulfonic Acid.- l-Methionine Ethyl Ester p-Toluenesulfonate.- 2.3 Benzyl Esters.- Glycine Benzyl Ester p-Toluenesulfonate.- tert-Butyloxycarbonyl-l-asparagine Benzyl Ester.- l-Glutamic Acid ?-Benzyl Ester.- 2.3.1 Polymeric Benzyl Esters.- Hydroxymethyl-Polymer.- tert-Butyloxycarbonyl-glycyl Resin.- Benzyloxycarbonyl-l-isoleucyl-Polymer.- 2.4 4-Nitrobenzyl Esters.- l-Alanine-4-Nitrobenzyl Ester p-Toluenesulfonate.- 2.5 4-Methoxybenzyl Esters of N?-Protected Amino Acids.- Benzyloxycarbonylglycine 4-Methoxybenzyl Ester.- 2.6 Benzhydryl Esters (Diphenylmethyl Esters).- 2.7 Phthalimidomethyl Esters.- 2.8 tert-Butyl Esters.- Addition of N?-Acylamino Acids to Isobutylene.- l-Proline tert-Butyl Ester.- Transesterification with tert-Butyl Acetate.- Esterification of Free Amino Acids through Acid Catalyzed Addition to Isobutylene.- l-Tyrosine tert-Butyl Ester.- 2.9 Phenacyl Esters.- Benzyloxycarbonylglycine Phenacyl Ester.- 2.10 2-Trimethylsilylethyl Esters.- 2.11 4-Picolyl Esters.- Benzyloxycarbonyl-l-phenylalanine 4-Picolyl Ester.- Benzyloxycarbonyl-l-valine 4-Picoly1 Ester.- 2.12 9-Fluorenylmethyl Esters.- tert-Butyloxycarbonyl-l-phenylalanine 9-Fluorenylmethyl Ester.- 2.13 2-Benzyloxyphenyl Esters.- l-Alanine 2-Benzyloxyphenyl Ester Hydrochloride.- 2.14 Phenyl Esters.- 2.15 Allyl Esters.- 3 Protection of Side Chain Functions.- 3.1 Serine Ethers.- N-tert-Butyloxycarbonyl-O-benzyl-l-Serine Cyclohexylammonium Salt.- 3.2 Ethers of Threonine.- O-tert-Butyl-l-threonine.- 3.3 Tyrosine Ethers.- O-Benzyl-l-tyrosine.- 3.4 Acylation of the ?-Amino Group of Lysine.- N?-Trifluoroacetyl-lysine 51.- N?-p-Toluenesulfonyl-l-lysine 52.- 3.5 Protection of the Guanidino Group of Arginine.- Nitro-l-arginine.- N?-Benzyloxycarbonyl-NG-p-toluenesulfonyl-l-arginine 54.- N?-Benzyloxycarbonyl-N?, N?-bis-(1-adamantyloxycarbonyl)-l-arginine 56.- N?-4-Methoxybenzyloxycarbonyl-NG-mesitylene-sulfonyl-l-arginine Cyclohexylammonium Salt 57.- NG-4-Methoxy-2, 3,6-trimethylbenzenesulfonyl-l-arginine 57.- 3.6 Masking the Imidazole in Histidine.- 3.6.1 Nim-p-Toluenesulfonyl-l-histidine.- N?-Benzyloxycarbonyl-Nim-tosyl-l-histidine 59.- 3.6.2 N?-tent-Butyloxycarbonyl-N?-benzyloxymethyl-l-histidine.- 3.6.3 Nim-Trityl-l-histidine.- 3.7 Blocking of the Indole Nitrogen in Tryptophan.- Nim-Formyl-l-tryptophan 62.- 3.8 Protection of Side Chain Carboxyl Groups.- l-Aspartic Acid ?-Benzyl Ester (?-Benzyl-l-aspartate).- l-Glutamic Acid ?-tert-Butyl Ester.- 3.9 Protection