The proposed work involves the development of new amino-protecting groups for use in the synthesis of sensitive, biologically active materials such as pharmaceuticals, peptides, proteins and polynucleotides. For ease of operation following the deblocking procedure, emphasis is placed on amino-protecting groups leading to (a) volatile, (b) totally insoluble or (c) infinitely water-soluble by-products. Because many acid-deblocked systems are currently available, emphasis is placed on groups deblocked by mild bases or by means of solvolytic reactions. The former category includes the 9-fluorenylmethyloxycarbonyl group as well as the 2,7-disubstituted analogs and related sulfones, sulfoxides and nitriles. A whole family of protective groups based on the specific fluoride ion cleavage of the beta-trimethylsilylethyloxycarbonyl group will be examined. The latter includes halo urethanes and the corresponding amides which are capable of undergoing """"""""self-cleavage"""""""" reactions in polar solvents or under physiological conditions. Other systems capable of exhibiting potent neighboring group effects such as alkylthio urethanes will be examined in the same connection. Finally a new class of polymeric deblocking agents related to ion-exchange resins will be studied in the case of both new and classic amino-protecting groups. Such polymeric reagents would have the advantage of allowing simple filtration to remove both reagent and by-products and of eventually being adaptable to column operation.
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