Recently, photoinduced electron transfer (PET) reactions have been focused on the behavior of radical-ion species. Here, we review the PET reactions of azo compounds, especially azoalkanes. Ground state interactions between azoalkanes and cationic salts have been investigated. On the basis of these results, studies of CT band excitation and PET reactions are developed. There are two types of the PET reactions. One is the electron transfer from the excited molecules of azoalkanes to the ground state electron acceptor molecules, and the other is the electron transfer from the ground state molecules of azoalkanes to the excited electron acceptor molecules. Products via cation intermediates are given from the reactions of acyclic azoalkanes and rearranged products are produced from the reaction of cyclic azo compounds. In many cases, it is known the back electron transfer plays very important role in the PET reaction.
Brevetoxin B (1), isolated from dinoflagellate, Gymnodinium breve Davis, has been known as a potent neurotoxin which affect to the current of Na ion of the Na channel. The total synthesis of this complex compound that includes 11 trans-fused rings and 23 stereocenters was completed under the conduction of Prof. Nicolaou in 0.043% total yield (91% average yields) from 2-deoxy-D-ribose after more than 10 years struggle. I herein wish to report the strategies and synthetic routes, both failed and successful, toward this destination.
HF-κB, HIV-EP1 Sp1, and TBP-E1A are transcriptional proteins involved in the long terminal repeat-directed expression of human immunodeficiency virus. Inhibitory effect of eighteen compounds against NF-κB, HIV-EP1, Sp1, and E1A was studied. The compounds could be classified into six types based on the inhibitory profile. Compounds of class A (ent-2, 11, 12, 13) and B (7, 9) are inhibitory against HIV-EP1. Class B compounds are more potent. Class C (14) compound is a Spl inhibitor. Compounds of D class (1, ent-1, 2) and E (5, 6, 8, 10) are inhibitors of both HIV-EP1 and Sp1. Class E compounds are more potent. NF-κB, HIV-EP1, and Sp1 are all inhibited by class F compounds (3, 4). Zinc complexes of class F compounds inhibit NF-κB without affecting zinc finger proteins. Relevant combination of these inhibitors would allow us to inhibit NF-κB, HIV-EP1, and Sp1 in any combinations.
Recently, inositol phospholipids in the plasma membrane have received much attention due to their biological interests in signal transduction systems. In order to accomplish efficient syntheses of the target lipids, a selective phosphorylation methodology via phosphonium salt and glycosylation method using glycosyl phosphite as a glycosyl donor were developed based on the phosphite chemistry. New benzoyl derivatives bearing oxyethyl substituents at the ortho position, so called PAC were devised for protecting hydroxyl groups. They can be removed chemoselectively by an intramolecular cyclization mode even in the presence of an acyl group and also function as an auxiliary in the diastereoselective acylation using a monomethyl tartrate derivative. Employing these synthetic strategies, synthesis of phosphatidylinositol 3, 4, 5-trisphosphate, 4, 5-bisphosphate, and 2, 6-dimannopyranosylphosphatidylinositol were achieved in an efficient and concise manner.
In order to realize an efficient enantioselective reaction through a catalytic process, we were interested in modifying a Lewis acid by electron-withdrawing chiral ligands. In such a modified Lewis acid, the chiral ligand will not only provide a chiral environment, but also increase the acidity of Lewis acid. Among various electron-withdrawing groups we selected C2-symmetric disulfonamide as a chiral ligand considering both electronic and steric characters. We developed (1) alkylation of aldehydes catalyzed by disulfonamide-Ti (O-i-Pr) 4-dialkylzinc system, and (2) the first Simmons-Smith type cyclopropanation of allylic alcohols by Et2Zn-CH2I2-disulfonamide or Et2Zn-CH2I2-disulfonamide-Al system. The concept of modifying Lewis acid by electron-withdrawing chiral ligand will be helpful in developing other type of catalytic and enantioselective reactions.
The thermal reaction of the α, β-unsaturated aldehydes having an 2-alkenylamino moiety at the β-position gave the azepine derivatives in good to excellent yields. When these groups were a part of heterocycles, the azepine derivatives fused by the heterocyclic systems were obtained. The imines of the aldehydes also afforded the azepine derivatives. These azepine-ring formation could be regarded as the intramolecular carbonyl and imine ene reactions classified as a Type III ene reaction. Therein, the reactions proceeded in a highly stereoselective manner. The PM 3 calculations of the model reactions suggest that the azepine-ring formation is constituted of two consecutive orbital-allowed reactions; 1, 6 -hydrogen shift leading to conjugated azomethine ylides and 1, 7-electrocyclization of the azomethine ylides. The scope and limitations of the azepine-ring formation will be discussed.
Recently, we purified rat thrombopoietin (TPO) from the plasma of irradiated rats by using a quantitative in vitro assay and then determined its partial amino acid sequences. Based on the sequence information, we isolated a rat TPO cDNA, a human TPO cDNA and the human TPO gene. The human TPO protein comprises 353 amino acids, including a 21 amino acid residue signal peptide. The protein displays two domains, with an amino-terminal region essential for biological activity and a carboxyl-terminal region containing six potential sites for N-glycosylation. The expression of TPO mRNA is the highest in the liver among various tissues tested, indicating that the liver is the primary organ of TPO production. It is now evident that TPO is a lineage-dominant hematopoietic factor that primarily regulates megakaryocytopoiesis and thrombopoiesis. Data from in vitro studies have shown that TPO exhibits both megakaryocyte colony-stimulating and megakaryocyte maturation activities. In vivo, TPO or PEG-rHuMGDF (a truncated form of TPO, chemically modified with polythyelene glycol) markedly increases platelet production in normal animals. Administration of PEG-rHu-MGDF or TPO is highly effective in improving thrombocytopenia in myelosuppressed animal models, suggesting the therapeutic potential of this molecule.