The Total Synthesis of Human Relaxin

Preliminary work on relaxin, or rather on the relaxin perimeters, had built up such a “curiosity pressure” that the trials and tribu-lations of a total synthesis became the lesser problem. When a peptide chemist faces a new synthesis he will immediately divide the problem into two major categories, one the overall plan of development of a primary structure (fragment condensation versus synthesis by sequential addition of amino acids) and secondly the decision concerning semipermanent side chain protections that must be compatible with the overall plan. If, for example, repeated exposure to weak acid is part of the synthesis of the primary backbone, acid labile semipermanent protecting groups can only be used if they require a much stronger acid for cleavage (trifluoroacetic acid vs. hydrogen fluoride) and so on. We will describe the synthesis of relaxins, including the special problems, in detail so that a student may derive sufficient information from the general concept for the synthesis of other peptides under similar conditions. For that reason a few of the approaches that did not work will be useful. In chapter 9 the problem of proper documentation of syntheses will be discussed as well as the recording of this type of research for it to become part of the serious scientific literature.

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