Phenols-useful templates for the synthesis of bi-functional orthogonally protected dendron building blocks via solid phase Mitsunobu reaction

Bi-functional dendritic building blocks for convergent dendrimer growth were successfully synthesized from phenolic templates in the solid phase via a Mitsunobu reaction. Each arm of the dendron building block carries an orthogonally protected secondary amine along the arm, and a peripheral primary amine or phenol group (building block type 1) or a tertiary amine junction with orthogonally protected peripheral primary amine or carboxyl groups (building block type 2). The synthetic routes reported in this work are general and applicable for the preparation of diverse building blocks, controlling protection, arm length, and peripheral moieties. These novel dendron units can form unusual dendritic architectures by solid-phase chemistry, which may be incorporated into specific complex structures expanding the scope of dendrimer science.     

Surface reactions of 4-aminothiophenol with heterobifunctional crosslinkers bearing both succinimidyl ester and maleimide for biomolecular immobilization

Surface reactions of 4-aminothiophenol (4-ATP) with a series of heterogeneous crosslinkers containing both maleimide and succinimidyl ester groups were investigated with infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS). Two types of surface reactions exist: (1) for most crosslinkers, a dominant reaction of amine and succinimidyl ester gave homogeneous maleimide-pendant surfaces; (2) for other crosslinkers, a side reaction between amine and maleimide, accompanying the main reaction, yielded heterogeneous surfaces with two linking groups, maleimide and succinimidyl ester. A typical example for the second case is the reaction of surface amines with N-succinimidyl-6-maleimidylhexanoate (SMH). Finally, a peptide, H-Gly-Arg-Gly-Asp-Ser-Pro-Cys-OH (GRGDSPC), was immobilized on the SMH-derived surface as a bridging structure through two linkages, cysteine thioether and glycine amide.     

Synthesis of Differentially Protected Glucosamine Building Blocks and Their Evaluation as Glycosylating Agents

The modular assembly of heparin oligosaccharides requires glucosamine building blocks with amine protecting groups for α-selective glycosylations that can be readily removed. The synthesis of N-4-nitrobenzensulphonamide (nosyl)- and N-2,4-dinitrophenyl (DNP)-protected glucosamine building blocks and their evaluation as glycosylating agents is described. The N-nosyl-protected glucosamine building blocks were challenging to prepare and their glycosylations resulted in inseparable mixtures of products. The N-DNP-protected glucosamines, however, were readily synthesized and resulted in α-selective couplings to protected l-iduronic acid derivatives.     

Separation of polyethylene glycols and maleimide‐terminated polyethylene glycols by reversed‐phase liquid chromatography under critical conditions

The separation of polyethylene glycols and maleimide‐substituted polyethylene glycol derivatives based on the number of maleimide end‐groups under critical liquid chromatography conditions has been investigated on a reversed‐phase column. The critical solvent compositions for nonfunctional polyethylene glycols and bifunctional maleimide‐substituted polyethylene glycols were determined to be identical at about 40% acetonitrile in water on a reversed‐phase octadecyl carbon chain‐bonded silica column using mixtures of acetonitrile and water of varying composition as the mobile phase at 25°C. The maleimide‐functionalized polyethylene glycols were successfully separated according to maleimide functionality (with zero, one, two, or three maleimide end‐groups, respectively) under the critical isocratic elution conditions without obvious effect of molar mass. The separation was mainly due to the hydrophobic interaction between the maleimide end‐groups and the column packing. Off‐line matrix‐assisted laser desorption/ionization time of flight mass spectrometry was used to identify the repeating units and, especially, the end‐groups of the maleimide‐substituted polyethylene glycols. Liquid chromatography analysis at critical conditions could provide useful information to optimize the synthesis of functional polyethylene glycols. To our knowledge, this is the first report of the baseline separation of maleimide‐functionalized polyethylene glycols based on the functionality independent of the molar mass without derivatization by isocratic elution.     

Synthesis and applications of masked oxo-sulfinamides in asymmetric synthesis

This short perspective reports on the synthesis and applications of a class of chiral amino carbonyl compounds, masked oxo-sulfinamides where the amine is protected with an N-sulfinyl moiety and the carbonyl group is protected as the ketal or 1,3-dithiane. These polyfunctionalized chiral building blocks are prepared by addition of organometallic reagents to masked oxo-sulfinimines (N-sulfinyl imines) or the addition of oxo-organometallic reagents and lithio-1,3-dithianes to sulfinimines. Because unmasking of the amino and carbonyl groups results in cyclic imines, these chiral building blocks are particularly useful for the asymmetric synthesis of functionalized nitrogen heterocycles, including prolines, pipecolic acids, pyrrolidines, homotropinones, tropinones, and tropane alkaloids such as cocaine and C-1 cocaine analogues.     

Novel redox active bifunctional crosslinkers from unsymmetrical 1,1′-disubstituted ferrocenes

The synthesis and electrochemistry of novel redox active bifunctional crosslinkers bearing pendant amine and maleimide groups from unsymmetrical 1,1′-disubstituted ferrocene precursors are reported.     

Maleimide‐based thiol reactive multiarm star polymers via Diels‐Alder/retro Diels‐Alder strategy

Multiarm star polymers containing thiol‐reactive maleimide groups at their core have been synthesized by utilization of atom transfer radical polymerization (ATRP) of various methacrylates using a masked maleimide containing multiarm initiator. One end of the initiator contains multiple halogen groups that produce the star architecture upon polymerization and the other end contains a masked maleimide functional group. Unmasking of the maleimide group after the polymerization provides the thiol reactive maleimide core that is widely used in bioconjugation. Functionalization of the core maleimide group with a thiol containing tripeptide was used to demonstrate facile reactivity of the core of these multiarm polymers under reagent‐free conditions. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2546–2556, 2010     

Isa‒NHC‒catalyzed intermolecular Stetter reaction of aromatic aldehydes with maleimides: An efficient access to 3‒aroylsuccinimides

An intermolecular Stetter reaction of aromatic aldehydes with maleimides has been developed using thiazolylidene salt derived Isa?NHC as an efficient organocatalyst. The synthesized Stetter products “3?aroylsuccinimides” are important building blocks for the synthesis of natural products and bioactive compounds. The reaction conditions are mild, and various substituents on aromatic aldehyde and maleimide nitrogen were tolerated.     

Synthesis of Functionalized Mono‐, Bis‐, and Trisethynyltriptycenes for One‐Dimensional Self‐Assembly on Surfaces

This paper describes the synthesis of triptycene‐based building blocks that are able to interact through hydrogen bonds to form one‐dimensional self‐assembled motifs on surfaces. We designed 9,10‐diethynyltriptycene derivatives functionalized at the ethynyl end groups by a variety of hydrogen‐bonding groups for homomolecular recognition and complementary building blocks for heteromolecular recognition. We also present the synthesis of bis‐ and trisethynyltriptycenes with terminal alkyne functional groups available for on‐surface azide–alkyne cycloaddition reaction to expand the potential of the triptycene building block.     

Orthogonal Synthesis of Xeno Nucleic Acids

Sequence‐defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid‐phase orthogonal “AB+CD” iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper‐catalyzed azide–alkyne cycloaddition (CuAAC) and acid–amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks).     

Synthesis of optically active bifunctional building blocks through enantioselective copper-catalyzed allylic alkylation using Grignard reagents

Enantioselective copper-catalyzed allylic alkylations were performed on allylic bromides with a protected hydroxyl or amine functional group using several Grignard reagents and Taniaphos L1 as a ligand. The terminal olefin moiety in the products was transformed into various functional groups without racemization, providing facile access to a variety of versatile bifunctional chiral building blocks.     

Stereoselective Mn-mediated coupling of functionalized iodides and hydrazones: a synthetic entry to the tubulysin gamma-amino acids

[structure: see text] Synthesis of gamma-amino acids, important building blocks in bioorganic and natural product chemistry, is accomplished using a stereoselective carbon-carbon bond construction of the chiral amine. Alkyl iodides and chiral hydrazones with protected alcohol functionality are coupled via highly diastereoselective photolytic Mn-mediated addition to the C=N bond, providing access to enantiomerically pure multifunctional chiral alpha-branched amines. Reductive N-N bond cleavage and alcohol oxidation provides alpha-substituted gamma-amino acid building blocks for tubulysin D.     

Maleimide‐Modified Phosphonium Ionic Liquids: A Template Towards (Multi)Task‐Specific Ionic Liquids

The synthesis and characterization of several compounds representing a new class of multitask‐specific phosphonium ionic liquids that contain a maleimide functionality is reported. The maleimide moiety of the ionic liquid (IL) is shown to undergo Michael‐type additions with substrates containing either a thiol or amine moiety, thus, serving as a template to introduce wide structural diversity into the IL. Multitask‐specific ILs are accessible by reaction of the maleimide with Michael donors that are capable of serving some function. As a model example to illustrate this concept, a redox active ferrocenyl thiol was incorporated and examined by cyclic voltammetry. Because the maleimide moiety is highly reactive to additions, the task‐specific ionic liquids (TSILs) are prepared as the furan‐protected Diels–Alder maleimide. The maleimide moiety can then be liberated when required by simple heating.     

Three component ketocoumarin, amine, maleimide photoinitiator I

An N-substituted maleimide has been used in conjunction with ketocoumarins and a tertiary amine to initiate the polymerization of 1,6-hexanedioldiacrylate in both the UV (365/366 nm) and visible region (436 nm) of the electromagnetic spectrum. The rate of polymerization of three ketocoumarin/tertiary amine combinations are significantly increased by the addition of a N-substituted maleimide, presumably due to oxidation of the coumarin ketyl radical formed by interaction between the triplet state of the ketocoumarin and the tertiary amine.     

Determination of polyethylene glycol end group functionalities by combination of selective reactions and characterization by matrix assisted laser desorption/ionization time-of-flight mass spectrometry

End groups play a critical role in macromolecular coupling reactions for building complex polymer architectures, yet their identity and purity can be difficult to ascertain using traditional analytical technique. Recent advances in mass spectrometry techniques have made matrix-assisted laser desorption/ionization time-of-fight (MALDI-TOF) mass spectrometry a rapid and powerful tool for providing detailed information about the identity and purity of homopolymer end groups. In this work, MALDI-TOF mass spectrometry was used to study end groups of linear polyethylene glycols. In particular, the identifications of alcohol, amine and thiol end groups are investigated because these nucleophilic moieties are among the most common within biological and synthetic macromolecules. Through comparative characterization of alcohol, amine, and thiol end groups, the exact identification of these end groups could be confirmed by selective and quantitative modification. The precision of this technique enables the unambiguous differentiation of primary amino groups relative to hydroxyl groups, which differ by only 1 mass unit. In addition, the quantitative conversion of various polyethylene glycol end groups using highly efficient coupling reactions such as the thiol-ene and azide-alkyne click reactions can be confirmed using MALDI-TOF mass spectrometry.     

Peptide-functionalized polyphenylene dendrimers

This contribution describes the synthesis of polyphenylene dendrimers that are functionalized with up to 16 lysine residues or substituted with short peptide sequences composed of 5 lysine or glutamic acid repeats and a C- or N-terminal cysteine residue. Polyphenylene dendrimers were prepared via a sequence of Diels-Alder cycloaddition and deprotection reactions from cyclopentadienone building blocks. Single amino acids could be introduced on the periphery of the dendrimers by using amino acid substituted cyclopentadienones in the last Diels-Alder addition reaction. Alternatively, peptide sequences were attached via a chemoselective reaction, which involved the addition of the sulfhydryl group of a cysteine residue of an oligopeptide to a maleimide moiety present on the surface of the dendrimer. These amino acid and peptide functionalized dendrimers may be of interest as model compounds to study DNA complexation and condensation or as building blocks for the preparation of novel supramolecular architectures via layer-by-layer self-assembly.     

Design Strategies for Shape-Persistent Covalent Organic Polyhedrons (COPs) through Imine Condensation/Metathesis

A series of dialdehyde compounds were synthesized and reacted with the complementary triamines (either planar or pyramidal with a 109.5° vertex) in a 3:2 ratio to explore the structural requirements on the building blocks for the successful construction of shape-persistent, covalent organic polyhedrons (COPs). Structural variations in the building blocks included the distance and angle between the two reactive sites (aldehyde or amine functional groups) and the absence/presence of solubilizing chains. Computer modeling was utilized to determine and compare the thermodynamic stabilities of some of these COP structures. Furthermore, gas adsorption studies were performed to explore the potential of these molecular cages for gas separation, particularly carbon capture, applications.     

Synthesis and polymerization of functionalized dendritic macromonomers

The synthesis of dendritic building blocks (dendrons) of the first generation (G1) and the second generation, which carry differently protected amine groups in the periphery, is reported. The dendrons are used for the synthesis of the corresponding acrylic and methacrylic macromonomers. Their polymerization behavior under radical conditions is investigated. The G1 dendronized polymers are decorated at their peripheral amino groups, that is, with the chiral amino acid L -phenylalanine by the attach-to approach. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1940–1954, 2001     

Fluorine-containing agrochemicals in the last decade and approaches for fluorine incorporation

In this review, the methodologies for fluorine incorporation of 40 fluorine-containing agrochemicals that received an international standardization organization(ISO) name during the last decade are described.The predominant approach for fluorine introduction of these agrochemicals is to use a fluorine-containing building block. Here we present how the fluorine-containing building blocks are introduced into these agrochemicals. The synthetic methods of fluorine-containing building blocks that are...     

Linear synthesis of the tumor-associated carbohydrate antigens Globo-H,SSEA-3, and Gb3

The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were synthesized in a linear fashion using glycosyl phosphate monosaccharide building blocks. All of the building blocks were prepared from readily available common precursors. The difficult alpha-(1-->4-cis)-galactosidic linkage was installed using a galactosyl phosphate donor with high selectivity. Introduction of the beta-galactosamine unit required the screening a variety of amine protecting groups to ensure good donor reactivity and protecting group compatibility. An N-trichloroacetyl-protected galactosamine donor performed best for the installation of the beta-glycosidic linkage. Conversion of the trichloroacetyl group to the N-acetyl group was achieved under mild conditions, fully compatible with the presence of multiple glycosidic bonds. This synthetic strategy is expected to be amenable to the synthesis of the globo-series of tumor antigens on solid-support.