Synthesis of Poly(amidoamine) Dendrimer with a Diphenyl Diselenide Core

Abstract

We succeeded in the synthesis of a novel poly(amidoamine) dendrimer having diphenyl diselenide at the core. Modification of the dendrimer diselenide by the reaction with glucono-δ-lactone in methanol gave a water-soluble dendrimer diselenide having chiral terminal groups. The structures of dendrimers were satisfactorily confirmed by MAIDI-TOF MS spectrometry, elemental analysis, and NMR spectroscopy. Interestingly, induced circular dichroism (ICD) of the interaction between the diphenyl diselenide core and D-gluconamide periphery of the dendrimer was observed at 300 nm.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT     

Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Succinyl‐cycloSal‐phosphate triesters of ribo‐ and 2′‐deoxyribonucleosides were attached to aminomethyl polystyrene as an insoluble solid support and reacted with phosphate‐containing nucleophiles yielding nucleoside di‐ and triphosphates, nucleoside diphosphate sugars, and dinucleoside polyphosphates in high purity after cleavage from the solid support. Here, reactive cycloSal‐phosphate triesters were used as immobilized reagents that led to a generally applicable method for the efficient synthesis of phosphorylated biomolecules and phosphate‐bridged bioconjugates.     

Efficient Formation of Luminescent Lanthanide(III) Complexes by Solid‐Phase Synthesis and On‐Resin Screening

Time‐resolved luminescence measurements of luminescent lanthanide complexes have advantages in biological assays and high‐throughput screening, owing to their high sensitivity. In spite of the recent advances in their energy‐transfer mechanism and molecular‐orbital‐based computational molecular design, it is still difficult to estimate the quantum yields of new luminescent lanthanide complexes. Herein, solid‐phase libraries of luminescent lanthanide complexes were prepared through amide‐condensation and Pd‐catalyzed coupling reactions and their luminescent properties were screened with a microplate reader. Good correlation was observed between the time‐resolved luminescence intensities of the solid‐phase libraries and those of the corresponding complexes that were synthesized by using liquid‐phase chemistry. This method enabled the rapid and efficient development of new sensitizers for Sm^III, Eu^III, and Tb^III luminescence. Thus, solid‐phase combinatorial synthesis combined with on‐resin screening led to the discovery of a wide variety of luminescent sensitizers.     

Microwave‐Assisted Solid‐Phase Synthesis of Antifreeze Glycopeptides

Microwave‐assisted solid‐phase synthesis allows for the rapid and large‐scale preparation and structure–activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H‐[Ala‐Thr(Galβ1,3GalNAcα1→)‐Ala]_n‐OH, n=2–6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGP_n (n=2–6, degree of polymerization, DP=2–6, M_w=1257–3690 Da), syAFGP₅ (DP=5, M_w=3082 Da) and syAFGP₆ (DP=6, M_w=3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP₆ forms a typical poly‐L ‐proline type II helix‐like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C‐3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.     

Biology‐Oriented Combined Solid‐ and Solution‐Phase Synthesis of a Macroline‐Like Compound Collection

Macrolines constitute a class of natural products that has more than 100 members and displays diverse biological activities. These compounds feature a cycloocta[b]indole scaffold that represents an interesting target structure for biology‐oriented synthesis (BIOS). We have presented a solid‐phase synthesis of isomerically pure cycloocta[b]indoles by employing the Pictet–Spengler reaction and the Dieckmann cyclization as key steps. The scope of this reaction sequence was investigated in more detail by using various additional diversification procedures, such as Pd‐catalyzed Sonogashira or Suzuki couplings on a solid phase, thus allowing, for example, the generation of 10‐substituted cycloocta[b]indole derivatives. Finally, solution‐phase decoration of the cycloocta[b]indole skeleton by reduction and saponification was evaluated, thereby further extending the scope of the solid‐phase synthesis.     

Efficient Solid‐Phase Synthesis of Sulfotyrosine Peptides using a Sulfate Protecting‐Group Strategy

Double protection : Efficient Fmoc‐based solid‐phase synthesis (SPPS) of sulfotyrosine (sY) peptides is achieved by incorporating the sY residue(s) as a dichlorovinyl‐protected (DCV) sulfodiester(s) and using 2‐methylpiperidine for Fmoc removal. After removal of the other protecting groups, the DCV group could be cleaved by mild hydrogenolysis giving the sY peptides in good yield.

     

Automated Solid‐Phase Synthesis of a β‐(1,3)‐Glucan Dodecasaccharide

β‐Glucans are a group of structurally heterogeneous polysaccharides found in bacteria, fungi, algae and plants. β‐(1,3)‐D ‐Glucans have been studied in most detail due to their impact on the immune system of vertebrates. The studies into the immunomodulatory properties of these glucans are typically carried out with isolates that contain a heterogeneous mixture of polysaccharides of different chain lengths and varying degrees of branching. In order to determine the structure–activity relationship of β‐(1,3)‐glucans, access to homogeneous, structurally‐defined samples of these oligosaccharides that are only available through chemical synthesis is required. The syntheses of β‐glucans reported to date rely on the classical solution‐phase approach. We describe the first automated solid‐phase synthesis of a β‐glucan oligosaccharide that was made possible by innovating and optimizing the linker and glycosylating agent combination. A β‐(1,3)‐glucan dodecasaccharide was assembled in 56 h in a stereoselective fashion with an average yield of 88 % per step. This automated approach provides means for the fast and efficient assembly of linker‐functionalized mono‐ to dodecasaccharide β‐(1,3)‐glucans required for biological studies.