Alkyl- and alkenylcobaloximes are conveniently prepared by the reaction of cobaloxime (I) with alkyl halides, vinyl halides, and acetylenes. The organocobaloximes thus obtained are convenient and versatile radical source for organic syntheses. The cobaloxime group is conveniently transformed into other functions by a variety of radicophiles. The organo radical from organocobaloxime attacks intramolecular or intermolecular olefin in the same manner as a general organo radical. Contrary to the conventional tin hydride method, an organocobaloxime gives not a reduction product but an olefinic product. The olefinic function thus formed is useful for further chemical transformation. The coexisting cobaloxime (II) radical modifies reactivity of the olefinic and arenic part of the organo radical containing sulfur function. The cobaloxime moiety activates an intramolecular diene and arene system to cause cycloaddition and aromatic substitution respectively.
Glycamino acids are C-glycoside derivatives that possess a C-1 carboxylate and an amino group replacing one of the hydroxyl groups of the monosaccharide moiety. For their preparation, an efficient α-stereoselective C-glycosyl cyanation procedure has been developed by an ethylthio glycoside and TMSCN in the presence of MeOTf. Assembly of oligomers composed of glycamino acid and of hybrid composed of glycamino acid and β-amino acid was carried out in a manner similar to that used for peptide synthesis. Those oligomers were found to be potent inhibitors of HIV infection, sialyl Lewis X -selectin interaction and tumor cell invasion in a sequence specific manner.
This article describes our recent development of completely synthetic vaccines based on tumour- and HIV-associated carbohydrate and peptide antigens having N-tetradecanoyl L-seryl-β-alanine-containing D-glucosamine derivatives structurally related to lipid A as efficient synthetic immunoadjuvants.
Based on the recent development of recombinant techniques, the investigation of biofunctional machinery at their ligand accepting interfaces has become a challenging and important subject of organic chemistry in the oncoming new century. Three major approaches currently used for structural biology have their own advantages and limitations. Spectroscopic methods are useful for analyzing ligand-receptor interactions at the atomic level. These approaches, however, usually require a significant amount of stable and pure proteins. Protein engineering based on gene technologies provides a series of mutants for the structural analysis of functional sites. One prerequisite for the use of this methods is that the mutants must, to a large extent, retain the conformation of the native receptors. Photoaffinity labeling, one of the third independent approach, has become increasingly appreciated as a powerful chemical methodology for the detailed structural analysis of ligand binding domains. The technique of photoaffinity labeling is a reliable chemical method which should be considered as being complementary to, rather than in competition with, the other two approaches. This review is focusing the recent application of photoaffinity labeling for probing the functional structure of ion channels, receptors, and enzymes.
The strategies for the development of fluorescent derivatization reagents for highly sensitive analysis of biomolecules, for example AE-OTf for carboxylic acids, (S) -2A1P-OTf for chiral carboxylic acids having chiral center at the remote position from carboxyl group and (S) -TBME carboxylic acid for “on-line HPLC-exciton CD analysis” of vicinal diols, diamines, and amino alcohols are discussed.
Synthesis and inclusion phenomena of nitrogen-bridged macrocyclic host molecules 1-4 and related macrocyclic compounds 5-7 are summarized. The new class of macrocycles 1-4 were designed and synthesized by one-step coupling reactions. Cubic cyclophane 5 was also obtained by this method. Because of the preorganized structure of 3 and 4 with four and six pyridine donors, respectively, they strongly bind proton, alkali metal and ammonium ions. They also act as a Cl- ion receptor in acidic solution. The compound 6 formed inclusion complexes with guanidium ion, urea and water molecules. Compounds 3 and 4 formed stable Cu+ or Ag+ complexes. The dinuclear complex 2 Ag+ ⊂4 has a short Ag+…Ag+ distance (2.78 Å). The halide anions (Cl-, Br-, I-) removed one Ag+ from 2 Ag+⊂4 to give Ag+ ⊂ 4, but further demetallation did not occur. Both silver complexes are stable to sunlight. The preparations of guest-free hosts were achieved by treating Cu+ ⊂3 or 2 Ag+ ⊂ 4 with CN-. Inclusion of neutral guests (NH3, BH3) was attempted using these guest-free hosts.