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.

I Introduction

II Protecting Groups
1 Introduction of Amine Protecting Groups
2 Blocking of the ?-Carboxyl Group
3 Protection of Side Chain Functions
III Activation and Coupling
1 The Acid Chloride Procedure
2 The Azide Process
3 Symmetrical Anhydrides
4 Mixed Anhydrides
5 Preparation of Active Esters
6 Coupling with Active Esters
7 Peptide Bond Formation with the Aid of Coupling Reagents
IV Removal of Protecting Groups
1 Hydrogenation
2 Reduction with Sodium in Liquid Ammonia
3 Removal of the Phthalyl (Phthaloyl) Group by Hydrazinolysis
4 Acidolysis
5 Hydrolysis
6 Base Catalyzed Elimination
7 Nucleophilic Displacement
8 Iodolysis
9 Reduction of Methionine Sulfoxide Containing Peptides
V Special Procedures
1 Ammonolysis of Esters
2 Transesterification
3 Cyclization
4 Polycondensation
5 Partial Synthesis
VI Models for the Study of Racemization
1 Benzoyl-leucyl-glycine Ethyl Ester
2 The Anderson-Callahan Test
3 Acylation with Acetyl-l-isoleucine
4 The Izumiya-Muraoka Model
5 Synthesis and Enantioselective Enzymic Hydrolysis of Tetraalanine
VII Reagents for Peptide Synthesis
1 tert-Butyl Azidoformate
2 1-Adamantyl Chlorocarbonate
3 1-Isobutyloxycarbonyl-2-isobutyloxy-1,2-dihydroquinoline (IIDQ)
4 Diphenyl Phosphorazidate (Diphenylphosphoryl Azide, DPPA)
5 3-Hydroxy-3,4-dihydroquinazoline-4-one (4-Hydroxyquinazoline 3-oxide)
6 1-Hydroxybenzotriazole
7 Ethyl 2-hydroximino-2-cyanoacetate
8 1-Guanyl-3,5-dimethyl-pyrazole Nitrate
VIII Appendix
1 Conversion of Dicyclohexylammonium Salts of Protected Amino Acids to the Free Acids
2 Preparation pf Analytical Samples.