Structure of tecophilin,a tri-caffeoylanthocyanin from the blue petals of Tecophilaea cyanocrocus, and the mechanism of blue color development

The pigment, tecophilin, in blue flowers of Tecophilaea cyanocrocus was isolated and the structure was determined to be 3-O-(6-O-α-l-rhamnopyranosyl-β-d-glucopyranosyl)-7-O-(6-O-(4-O-(2-O-(4-O-β-d-glucopyranosyl-(E)-caffeoyl)-6-O-(4-O-β-d-glucopyranosyl-(E)-caffeoyl)-β-d-glucopyranosyl)-(E)-caffeoyl)-β-d-glucopyranosyl)delphinidin. The reproduction experiment of the same color as petals according to the results of chemical analysis and measurement of vacuolar pH of blue cells clarified that the blue color solely develops by tecophilin without interaction of metal ions nor co-pigments. ¹H NMR analysis and CD spectrum indicate the co-existence of clockwise intermolecular self-association of the delphinidin nuclei and intramolecular π–π stacking between the chromophore and caffeoyl residues to derive bathochromic shift of the absorption spectrum and stabilize the color by preventing hydration reaction.     

Enantioselective Total Synthesis of Pinnaic Acid and Halichlorine

The enantioselective total synthesis of the bioactive marine natural products pinnaic acid and halichlorine is reported in detail. Our total synthesis features the construction of the five‐membered ring and C9 and C13 stereogenic centers through a palladium‐catalyzed trimethylenemethane [3+2] cyclization; the installation of the nitrogen atom through a regioselective Beckmann rearrangement of a poorly reactive ketone; the stereoselective cyclization of the spiro ring through a four‐step, one‐pot hydrogenation–cyclization; and efficient connection of the sterically hindered lower chain through a reduced‐pressure cross olefin metathesis reaction.     

The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro

Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Following 9 days of culture with SL-13R, the numbers of total cells, CD34+, CD38− cells, and hematopoietic stem cell (HSC)-enriched cells were significantly increased relative to control. Transplantation of cells cultured with SL-13R into immunodeficient NOD/Shi-scid/IL-2Rγ knockout mice confirmed that they possess long-term reconstitution and self-renewal ability. AHNAK, ANXA2, and PLEC all interact with SL-13R. Knockdown of these genes in UCB CD34+ cells resulted in reduced numbers of hematopoietic colonies relative to SL-13R-treated and non-knockdown controls. In summary, we have identified a novel bioactive peptide SL-13R promoting expansion of UCB CD34+ cells with long-term reconstitution and self-renewal ability, suggesting its clinical use in the future.     

Synthesis of New Chlorin e6 Trimethyl and Protoporphyrin IX Dimethyl Ester Derivatives and Their Photophysical and Electrochemical Characterizations

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e₆ trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn^II complexes. The synthesis of these molecules linked at the β‐pyrrolic positions to pyrano[3,2‐c]coumarin, pyrano[3,2‐c]quinolinone, and pyrano[3,2‐c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels–Alder reaction. The α‐methylenechromanes, α‐methylenequinoline, and ortho‐quinone methides were generated in situ from a Knoevenagel reaction of 4‐hydroxycoumarin, 4‐hydroxy‐6‐methylcoumarin, 4‐hydroxy‐N‐methylquinolinone, and 2‐hydroxy‐1,4‐naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn^II complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time‐correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn^II complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn^II complexes were also carried out to gain insights into their behavior for such applications.     

Control of Chromophore Symmetry by Positional Isomerism of Peripheral Substituents

The first example of the control of porphyrinoid chromophore symmetry based on the positional isomerism of peripheral substituents has been achieved by preparing tetraazaporphyrins (TAPs) with C_4h, D_2h, C_2v, and C_s symmetry due to the relative arrangement of peripheral tert‐butylamino and cyano groups as push and pull substituents, respectively. The four structural isomers were successfully isolated and characterized by ¹H NMR spectroscopy and X‐ray crystallography. The band morphology in the Q‐band region varies depending on the molecular symmetry due to the significant perturbation introduced into the chromophore by the push and pull substituents. The C_4h and C_2v isomers exhibit a single Q band, whereas the Q bands of the D_2h and C_s isomers show a marked splitting. The magnetic circular dichroism spectra indicate that the push–pull TAPs retain the properties of the 16‐membered 18π‐electron perimeter generally observed for porphyrinoids. Theoretical calculations have demonstrated that the perturbation introduced by the substituents lowers the D_4h symmetry of the parent TAP π‐conjugated system, and this results in significant spectral changes. A novel approach to the fine‐tuning of the spectral properties of porphyrinoids based on changes in the chromophore symmetry is described.     

Serine‐Selective Aerobic Cleavage of Peptides and a Protein Using a Water‐Soluble Copper–Organoradical Conjugate

The site‐specific cleavage of peptide bonds is an important chemical modification of biologically relevant macromolecules. The reaction is not only used for routine structural determination of peptides, but is also a potential artificial modulator of protein function. Realizing the substrate scope beyond the conventional chemical or enzymatic cleavage of peptide bonds is, however, a formidable challenge. Here we report a serine‐selective peptide‐cleavage protocol that proceeds at room temperature and near neutral pH value, through mild aerobic oxidation promoted by a water‐soluble copper–organoradical conjugate. The method is applicable to the site‐selective cleavage of polypeptides that possess various functional groups. Peptides comprising D ‐amino acids or sensitive disulfide pairs are competent substrates. The system is extendable to the site‐selective cleavage of a native protein, ubiquitin, which comprises more than 70 amino acid residues.     

High Diastereoselection of a Dissymmetric Capsule by Chiral Guest Complexation

Encapsulation of chiral guests in the dissymmetric capsule 1?4 BF₄ formed diastereomeric supramolecular complexes G ? 1?4 BF₄ ( G : guest). When chiral guests 2 a – q were encapsulated within the dissymmetric space of the self‐assembled capsule 1?4 BF₄, circular dichroism (CD) was observed at the absorption bands that are characteristic of the π–π* transition of the bipyridine moiety of the capsule, which suggests that the P and M helicities of the capsule are biased by the chiral guest complexation. The P helicity of diastereomeric complex (S)‐ 2 l ? 1?4 BF₄ was determined to be predominant, based on CD exciton coupling theory and DFT calculations. The diastereoselectivity was highly influenced by the ester substituents, such that benzyl ester moieties were good for improving the diastereoselectivity. A diastereomeric excess of 98 % was achieved upon the complexation of 2 j . The relative enthalpic and entropic components for the distereoselectivity were obtained from a van’t Hoff plot. The enthalpic components were linearly correlated with the substituent Hammett parameters (σ_p⁺). The electron‐rich benzyl ester moieties generated donor–acceptor π–π stacking interactions with the bipyridine moiety, which resulted in a significant difference in energy between the predominant and subordinate diastereomeric complexes.     

Direct Asymmetric Mannich‐Type Reaction of α‐Isocyanoacetates with Ketimines using Cinchona Alkaloid/Copper(II) Catalysts

The enantioselective direct Mannich‐type reaction of ketimines with α‐isocyanoacetates has been developed. Excellent yields and enantioselectivity were observed for the reaction of various ketimines and α‐isocyanoacetates using cinchona alkaloid/Cu(OTf)₂ and a base. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. This process offers an efficient route for the synthesis of α,β‐diamino acids.