Amit Basu

Configurational stability and transfer of stereochemical information in the reactions of enantioenriched organolithium reagents

The conversion of a prochiral methylene group into a stereogenic center by means of a lithiation/substitution sequence has emerged as a powerful synthetic transformation over the past 15 years. This reaction proceeds via a chiral organolithium intermediate, and the stereochemical fidelity of the overall reaction sequence is intimately dependent on the stereochemical behavior of the chiral organolithium as well as on the rate and stereochemical sense of the electrophilic substitution step. Chiral organolithium reagents were first reported by Letsinger, Curtin, and Applequist half a century ago. The lithiated intermediates in these early studies were not highly configurationally stable, and applications in stereoselective synthesis were not immediately forthcoming. The two decades that followed the 1980 report by Still and Sreekumar of a configurationally stable alpha-oxyorganolithium were marked by an increased interest in these reagents. As the synthetic applications of chiral organolithium reagents have grown, so have accompanying mechanistic studies of these intermediates which serve as the basis for this review.

An efficient method for para-methoxybenzyl ether formation with lanthanum triflate

PMB ethers of alcohols are prepared in high yields and short reaction times using the trichloroacetimidate of PMB alcohol and lanthanum triflate. The mild conditions allow protection of acid-sensitive alcohols.

Konfigurative Stabilität und Stereoinformationstransfer in Reaktionen Enantiomeren‐angereicherter Organolithium‐Reagentien

In den letzten 15 Jahren ist die Leistungsfahigkeit der Umwandlung prochiraler Methylengruppen durch Lithiierung und anschliesende Substitution in Stereozentren deutlich geworden. Die Stereochemie der Gesamtreaktion hangt stark vom stereochemischen Verhalten der als Intermediat auftretenden chiralen Organolithium-Verbindung sowie der Geschwindigkeit und dem stereochemischen Verlauf der elektrophilen Substitution ab. Letsinger, Curtin und Applequist waren die ersten, die – bereits vor einem halben Jahrhundert – uber chirale Organolithium-Reagentien berichteten. Ihre lithiierten Intermediate waren konfigurativ allerdings nicht sehr stabil, daher war die Anwendbarkeit fur stereoselektive Synthesen zunachst gering. 1980 berichteten Still und Sreekumar dann von einer konfigurativ stabilen α-Oxy-Organolithium-Verbindung, und in den folgenden Jahrzehnten stieg das Interesse an diesen Reagentien. Mit dem zunehmenden Einsatz von chiralen Organolithium-Reagentien in Synthesen sind auch immer mehr begleitende mechanistische Untersuchungen durchgefuhrt worden, die als Basis fur diesen Aufsatz dienen.

Core Functionalization of Hollow Polymer Nanocapsules

Hollow nanoscale polymer capsules have found wide applications in drug delivery and catalysis. The use of nanocapsules and related materials for drug delivery, as nanoreactors, or as platforms for chemical separations requires control over cargo entry and exit and installation of diverse chemical functionality in the capsule interior. Despite the diversity of methods for nanocapsule preparation, methods for efficiently functionalizing the core of hollow nanocapsules are scarce. We report here a versatile and modular approach for the synthesis of hollow polymeric capsules that can be readily and diversely functionalized in the core. Capsules functionalized with pyrene, ferrocene, amines, and carboxylic acids have been prepared. The capsules are characterized using dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy. These core functionalized capsules can selectively extract hydrophilic cationic or anionic dyes into organic solutions based on the charge complementarity of the core functionality. The synthetic approach described here is modular and permits facile control of the interior as well as exterior properties of the nanocapsules.

Carbohydrate-Coated Fluorescent Silica Nanoparticles as Probes for the Galactose/3-Sulfogalactose Carbohydrate–Carbohydrate Interaction Using Model Systems and Cellular Binding Studies

The carbohydrates galactose and 3-sulfogalactose, found on sphingolipids in myelin, interact with each other via a carbohydrate-carbohydrate interaction (CCI). In oligodendrocytes, this interaction triggers a signaling cascade resulting in cytoskeletal rearrangements and reorganization of glycolipids and proteins at the cellular surface. These rearrangements can also be triggered by synthetic multivalent glycoconjugates. In this report, we describe the synthesis of glycan-coated silica nanoparticles and their subsequent binding to cultured oligodendrocytes and purified myelin. Fluorescent silica nanoparticles with an azidosiloxane-derived outer shell were functionalized with carbohydrates using the copper-promoted azide-alkyne cycloaddition reaction. The carbohydrate-carbohydrate interaction between galactose and 3-sulfogalactose was examined by measuring the binding of 3-sulfogalactose-containing nanoparticles to galactolipids that had been immobilized in a multiwell plate. Particle aggregation mediated by CCI was observed by TEM. The interaction of the particles with oligodendrocytes and purified myelin was examined using fluorescence microscopy, providing direct evidence for binding of galactose and 3-sulfogalactose-coated nanoparticles to oligodendrocytes and myelin fragments.

Probing the lactose.GM3 carbohydrate-carbohydrate interaction with glycodendrimers.

Multivalent glycoconjugates were prepared using generation-4 PAMAM dendrimers, and their interaction with Langmuir monolayers containing GM3 was investigated. Excessive carbohydrate valency adversely affects the carbohydrate-carbohydrate interaction. The GM3 monolayer selectively interacts with lactose-functionalized dendrimers in the presence of calcium ions.

Participation of galactosylceramide and sulfatide in glycosynapses between oligodendrocyte or myelin membranes

The two major glycosphingolipids of myelin, galactosylceramide (GalC) and sulfatide (SGC), interact with each other by trans carbohydrate–carbohydrate interactions. They face each other in the apposed extracellular surfaces of the multilayered myelin sheath produced by oligodendrocytes (OLs). Multivalent galactose and sulfated galactose, in the form of GalC/SGC‐containing liposomes or silica nanoparticles conjugated to galactose and galactose‐3‐sulfate, interact with GalC and SGC in the membrane sheets of OLs in culture. This stimulus results in transmembrane signaling, loss of the cytoskeleton and clustering of membrane domains, suggesting that GalC and SGC could participate in glycosynapses between apposed OL membranes or extracellular surfaces of mature myelin. Such glycosynapses may be important for myelination and/or myelin function.

Studies of the carbohydrate-carbohydrate interaction between lactose and GM3 using Langmuir monolayers and glycolipid micelles

This paper describes studies of the carbohydrate-carbohydrate interaction (CCI) between micelles of a lactosyl lipid and monolayers of the glycosphingolipid GM3. The lactose Lac·GM3 interaction is involved in B16 melanoma cell adhesion and signaling processes, and a thorough understanding of the molecular details of this CCI is important for the design of new anti-adhesive and anti-metastatic agents. In this paper, we examine the influence of variations in divalent cations and subphase ionic strength on the Lac·GM3 interaction. Our results indicate that, in the absence of divalent cations, the Lac·GM3 CCI is strengthened at higher sodium chloride concentrations in the subphase. In contrast, when divalent cations are present in solution, the CCI is not as sensitive to ionic strength. These results suggest a role for both cation dependent as well as independent interactions in the Lac·GM3 CCI. Published in 2004.

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide-alkyne cycloaddition.

Summary Functionalizable monotelechelic polymers are useful materials for chemical biology and materials science. We report here the synthesis of a capping agent that can be used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide–alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers.

Photo- and Biophysical Studies of Lectin-Conjugated Fluorescent Nanoparticles: Reduced Sensitivity in High Density Assays†

Lectin-conjugated, fluorescent silica nanoparticles (fNP) have been developed for carbohydrate-based histopathology evaluations of epithelial tissue biopsies. The fNP platform was selected for its enhanced emissive brightness compared to direct dye labeling. Carbohydrate microarray studies were performed to compare the carbohydrate selectivity of the mannose-recognizing lectin Concanavalin A (ConA) before and after conjugation to fluorescent silica nanoparticles (ConA-fNP). These studies revealed surprisingly low emission intensities upon staining with ConA-fNP compared to those with biotin-ConA/Cy3-streptavidin staining. A series of photophysical and biophysical characterizations of the fNP and ConA-fNP conjugates were performed to probe the low sensitivity from fNP in the microarray assays. Up to 1200 fluorescein (FL) and 80 tetramethylrhodamine (TR) dye molecules were incorporated into 46 nm diameter fNP, yielding emissive brightness values 400 and 35 times larger than the individual dye molecules, respectively. ConA lectin conjugated to carboxylic acid surface-modified nanoparticles covers 15-30% of the fNP surface. The CD spectra and mannose substrate selectivity of ConA conjugated to the fNP differed slightly compared to that of soluble ConA. Although, the high emissive brightness of fNP enhances detection sensitivity for samples with low analyte densities, large fNP diameters limit fNP recruitment and binding to samples with high analyte densities. The high analyte density and nearly two-dimensional target format of carbohydrate microarrays make probe size a critical parameter. In this application, fNP labels afford minimal sensitivity advantage compared to direct dye labeling.