Special Issue "Protecting Group in Organic Synthesis"

Guest Editor
Prof. Dr. Jyoti Chattopadhyaya
Department of Cell and Molecular Biology, Bioorganic Chemistry, Uppsala University, Biomedical Center Husargatan 3, Box 581 SE-751 23 Uppsala, Sweden
E-Mail:
Interests: synthesis; physico-chemistry; 1H; 13C; 15N; 31P-NMR spectroscopy of carbohydrates; nucleosides; nucleoside analogues; phosphorylation methods; nucleotides; nucleotide analogues; oligo-DNA; oligo-RNA; lariat- and branched-RNA; RNA catalysis; ribozyme; antisense; RNAi; siRNA; conformationally constrained nucleosides; tethers; protecting group chemistry; hydroxyl; amino; internucleosidyl phosphate; heterocyclic antibacterial compounds against multiresistant strains

Guest Editor
Dr. Andras Földesi
Department of Cell and Molecular Biology, Bioorganic Chemistry, Uppsala University, Biomedical Center, Husargatan 3, Box 581 SE-751 23; Uppsala Sweden
E-Mail:

Dear Colleagues,

Protecting groups play an instrumental role in the synthesis of complex organic molecules. This special issue is to cover the newest developments in the field reporting on new hydroxyl, amino, carbonyl, carboxyl and phosphate protecting groups or new ways of application of existing ones useful in the synthesis of biomolecules (such as carbohydrates, peptides and oligonucleotides) or other pharmacologically or industrially relevant compounds in solution or on solid phase.

Prof. Dr. Jyoti Chattopadhyaya
Dr. Andras Földesi
Guest Editors

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• protecting group
• temporary-permanent
• functional groups: amino, hydroxyl, carbonyl, carboxyl, phosphate
• introduction
• removal
• orthogonality
• compatibility
• mechanistic, rate consequences

Type of Paper: Review
Title: 9-Phenyl-9-fluorenyl Group for Nitrogen Protection in Chirospecific Synthesis
Authors: Essi J. Karppanen, Ari M.P. Koskinen
Affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aalto University, School of Science and Technology, PO Box 16100, Kemistintie 1, FI-00076 Aalto, Finland; E-Mail: ari.koskinen@tkk.fi (A.M.P.K.)
Abstract: One of the challenges in asymmetric synthesis is to prevent racemization of enantiopure starting materials. However, at least some of the enantiopurity is lost in the existing reactions used in synthetic organic chemistry. This translates into unnecessary material loss. Naturally enantiopure proteinogenic amino acids that can be transformed into many useful intermediates in drug syntheses, for example, are especially vulnerable to this. A relatively rarely used protecting group called phenylfluoren-9-yl (Pf) has proven to be able to prevent racemization in a-amino compounds. This review article showcases Pf-protected amino acid derivatives in chirospecific synthesis.

Type of Paper: Review
Title: Selenium Protecting Groups in Organic Chemistry: Special Emphasis on Selenocysteine Se-Protection in Solid Phase Peptide Synthesis
Author: Stevenson Flemer Jr.
Affiliation: Department of Biochemistry at the University of Vermont,, B415 Given Building, 89 Beaumont Drive, Burlington, VT, 05405, USA;
E-Mail: sflemer@uvm.edu
Abstract: The appearance of selenium in organic synthesis is relatively rare, and thus examples in the Literature pertaining to the masking of its considerable reactivity is similarly uncommon. Greene's Protecting Groups in Organic Synthesis, the standard bearer for the state of the art in this arena, offers no entries for selenium protective methodology, in stark comparison to its mention of the great variety of protecting groups germane to its chalcogen cousin sulfur. This scarcity of Se-protection makes it no less interesting and pertinent toward the construction of selenium-containing organic systems which do indeed require the iterative blocking and de-blocking of selenol functionality. A selenium-containing system which is especially relevant is Selenocysteine, as its use in Solid Phase Peptide Synthesis requires extensive protection of its selenol sidechain. This review will attempt to summarize the current state of understanding with regard to selenium protection protocol in organic synthesis. Moreover, it will provide a special emphasis on Selenocysteine sidechain protection, comprising both the breadth of functionality used for this purpose as well as methods of deprotection.

Type of Paper: Article
Title: Protection Possibilities in O-glycopeptide Synthesis
Authors: Anita Kovács ¹, Orsolya Hegyi ¹, Enikő Forró ², István Mándity ², László Kalmár ³, János Kerékgyártó ³ and Gábor K. Tóth ¹
Affiliations: ¹ University of Szeged, Faculty of Medicine, Department of Medical Chemistry, Szeged, Hungary
² University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, Szeged, Hungary
³ University of Debrecen, Faculty of Science and Technology, Institute of Biology and Ecology, Debrecen, Hungary;
E-Mail: tgabor@mdche.szote.u-szeged.hu (G.K.T.)
Abstract: Posttranslational modification (PTM) is essential for protein activation. Among the PTM, glycosylation is a major form of protein modification and 50% of human proteins are reported to be glycosylated. In spite of intensive investigation, the functions of those oligosaccharides have not yet been completely elucidated. It is therefore of great interest to synthesize glycopeptides. Currently, there are two approaches to synthesize glycopeptides including the convergent method and the building block method. The most challenging task in the building block approach the selection or elaboration of the appropriate protecting groups, since most of the routinely used side-chain protecting groups cannot be applicable in the glycopeptide chemistry. The first model what we used was the repetitive sequence of the aggrecan protein (Gly-Val-Glu-Asp-Ile-Ser*-Gly-Leu-Pro-Ser-Gly and Glu-Val-Leu-Glu-Thr*-Ala-Ala-Pro-Gly-Val-Glu-Asp (* site of glycosylation), where the protection of the side-functions of Glu, Asp, Ser and the glyco part (xylose) ought to be solved. We elaborated several protecting group combinations, which were successfully used for these peptides. The protection for Asp and Glu were 4-(N-(1-(4,4-dimethyl-2,6-dioxacyclohexylidene)-3-methylbutyl)amino)benzyl (Dmab) and allyl ester; benzyl and tert-butyl-dimethyl-silyl (TBDMS) ether for Ser and Thr. For the protection of the glyco moiety acetyl and benzoyl esters were used. The removal of the upper protecting groups were optimised. In order to work out protecting group combination for other trifunctional amino acids (Lys, His, Tyr, Thr and Arg) a new model, the Sp1 transcription factor was choosed. The DNA binding domain of Sp1 consist of three Cys2His2-type zinc finger motifs. Their 3D structures without glycosylation were identified with NMR spectroscopy and proved to be ββα motifs. The two target fragments having carbohydrate moiety were the followings: Lys-Arg-Phe-Met-Arg-Ser*-Asp-His-Leu-Ser*-Lys-His-Ile-Lys-Thr-His-Gln-Asn and Gly-Lys-Val-Tyr-Gly-Lys-Thr*-Ser*-His-Leu-Arg-Ala-His-Leu-Arg-Trp-His-Thr-Gly. The protection of the His, Tyr and Thr were carried out via their benzyl-derivatives. Lys was protected with 1-(4,4-dimethyl-2,6-dioxacyclohexylidene)ethyl (Dde) group. The application of these groups proved to be successful. In contrast of this, the protection of the guanidino-function of the Arg using all the commercially available derivatives failed. It seems to be the only possibility the application the 1,2-dimethylindolyl-3-sulphonyl (MIS) group, which was described recently and not commercially available yet. The glycosylated amino acid derivatives were prepared via Koenigs-Knorr glycosylation of the appropiately proteced hydroxy-amino acids.