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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM009706-20
Application #
3268047
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1976-06-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
20
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali et al. (2009) Dicyclopropylmethyl peptide backbone protectant. Org Lett 11:3718-21
Carpino, Louis A; Abdel-Maksoud, Adel Ali; Mansour, E M E et al. (2007) Segment Coupling to a Highly Hindered N-Terminal, Alamethicin-Related alpha-Aminoisobutyric Acid (Aib) Residue. Tetrahedron Lett 48:7404-7407
Carpino, Louis A; Abdel-Maksoud, Adel Ali; Ionescu, Dumitru et al. (2007) 1,1-dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (alpha-Nsmoc) and 3,3-dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (beta-Nsmoc) amino-protecting groups. J Org Chem 72:1729-36
McGinniss, M J; Kazazian Jr, H H; Stetten, G et al. (1992) Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21. Am J Hum Genet 50:15-28