21 Pages


Each of these reactions is known to be general and typically high yielding in solution, although one cannot predict how such reactions will translate to chemistry on a solid support. Thus, one or two reactions are carried out on a solid-supported starting material before running a set of 40 compounds, to ensure that appropriate conditions can be found. The actual synthesis of hydantoins was carried out as follows. Eight resins containing different protected amino acids were each placed into five gas dispersion tubes, affording a total of 40 reaction vessels. Deprotection as shown in step one afforded the corresponding amino acid-charged resins, now possessing free amine (-NH2) groups. Each resin-bound amino acid was then reacted with five different isocyanates (step two), to afford a total of 40 different ureas. In the final step, treatment of all reaction tubes with 6 M HCI and heat resulted in cyclative cleavage and release of the product hydantoins from the resin, which were dissolved individually in methanol, concentrated, and analyzed.