Silylated Sugars – Synthesis and Properties

Silicon has been used in carbohydrate chemistry for half a century, but mostly as a protective group for sugar alcohols. Recently, the use of silicon has expanded to functionalization via C–H activation, conformational arming of glycosyl donors, and conformational alteration of carbohydrates. Silicon has proven useful as more than a protective group and during the last one and a half decades we have demonstrated how it influences both the reactivity of glycosyl donors and stereochemical outcome of glycosylations. Silicon can also be attached directly to the sugar C-backbone, which has even more pronounced effects on the chemistry and properties of the molecules. In this Account, we will give a tour through our work involving silicon and carbohydrates.1 Introduction2 Conformational Arming of Glycosyl Donors with Silyl Groups3 Silyl Protective Groups for Tethering Glycosyl Donors4. Si–C Glycosides via C–H Activation4.1 C–H Activation and Oxidation of Methyl 6-Deoxy-l-glycosides4.2 Synthesis of All Eight 6-Deoxy-l-sugars4.3 Synthesis of All Eight l-Sugars by C–H Activation4.4 Modification of the Oxasilolane Ring5 C–Si in Glycosyl Donors – Activating or Not?6 Si–C-Substituted Pyranosides7 Perspective

Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5H)-one Derivatives

The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(5H)-one core. We describe a comprehensive characterization of obtained compounds with respect to their anticancer potency and selectivity towards cancer cells. All four novel compounds exert stronger antiproliferative activity than MBA. Moreover, 3b induce apoptosis in colon cancer cell lines. A detailed investigation of the mechanism of action revealed that 3b activity stems from the down-regulation of survivin and the activation of caspase-3. Furthermore, compound 3b attenuates the clonogenic potential of HCT-116 cells. Interestingly, we also found that depending on the type of the silyl group, compound selectivity towards cancer cells could be precisely controlled. Collectively, we demonstrated the utility of silyl groups for adjusting both the potency and selectivity of silicon-containing compounds. These data reveal a link between the types of silyl group and compound potency, which could have bearings for the design of novel silicon-based anticancer drugs.

Design, Synthesis, and Implementation of Sodium Silylsilanolates as Silyl Transfer Reagent

There is an increasing demand for facile delivery of silyl groups onto organic bioactive molecules. One of the common methods of silylation via a transition metal-catalyzed coupling reaction employs hydrosilane, disilane, and silylborane as major silicon sources. However, labile nature of the reagents or harsh reaction conditions sometimes renders them inadequate for the purpose. Thus, a more versatile alternative source of silyl groups has been desired. We hereby report a design, synthesis, and implementation of new storable sodium silylsilanolates that can be used for the silylation of aryl halides and pseudohalides in the presence of a palladium catalyst. The new method allows a late-stage functionalization of polyfunctionalized compounds with a variety of silyl groups. Mechanistic studies indicate that 1) a nucleophilic silanolate attacks a palladium center to afford a silylsilanolate-coordinated arylpalladium intermediate and 2) a polymeric cluster of silanolate species assists in the intramolecular migration of silyl groups, which would pro-mote an efficient transmetalation.<br>

Dual Temperature and Metal Salts-Responsive Interpenetrating Polymer Networks Composed of Poly (N-isopropylacrylamide) and Polyethylene Glycol

Novel interpenetrating polymer networks (IPNs) composed of poly(N-isopropylacrylamide) (poly-NIPAM) and polyethers—namely, polyethylene glycol (PEG) and poly(tetramethylene oxide)—were synthesized in the absence and presence of polysiloxane containing a silanol residue. Gelation was accomplished using end-capped polyethers with trimethoxysilyl moieties and proceeded through simultaneous radical gelation of NIPAM and condensation of the silyl groups to form siloxane linkages. Thus, a novel one-step method constructing an IPN structure was provided. The obtained IPNs showed a gentle temperature-responsive volume change in water owing to the constructed poly-NIPAM gel component. In addition, a specific color-change response to chemical stimuli, such as CuCl2 and AgNO3 in water, was observed only when both components of poly-NIPAM and PEG existed in a gel form. For example, a single network gel composed of poly-NIPAM or PEG was isolated as a pale blue hydrogel, whereas IPNs composed of poly-NIPAM and PEG components turned yellow after swelling in an aqueous CuCl2 solution (0.1 M, pale blue). Dual-responsive functionalities of the synthesized hydrogels to temperature and metal salts, along with volume and color changes, were demonstrated.

Bis-silylation of internal alkynes enabled by Ni(0) catalysis

Abstract1,2-Bis-silyl alkenes have exciting synthetic potential for programmable sequential synthesis via manipulation of the two vicinal silyl groups. Transition metal-catalyzed bis-silylation of alkynes with disilanes is the most straightforward strategy to access such useful building blocks. However, this process has some limitations: (1) symmetric disilanes are frequently employed in most of the reactions to assemble two identical silyl groups, which makes chemoselective differentiation for stepwise downstream transformations difficult; (2) the main catalysts are low-valent platinum group transition metal complexes, which are expensive; and (3) internal alkynes remain challenging substrates with low inherent reactivity. Thus, the development of abundant metal-catalyzed bis-silylation of internal alkynes with unsymmetrical disilanes is of significance. Herein, we solve most of the aforementioned limitations in bis-silylation of unsaturated bonds by developing a strongly coordinating disilane reagent and a Ni(0) catalytic system. Importantly, we sufficiently realize the stepwise recognition of the two silyl groups, making this synthetic protocol of wide potential utility.

Synthesis and X-ray characterization of 15- and 16-vertex closo-carboranes

Carboranes are a class of carbon-boron molecular clusters with three-dimensional aromaticity, and inherent robustness. These endowments enable carboranes as valuable building blocks for applications ranging from functional materials to pharmaceuticals. Thus, the chemistry of carboranes has received tremendous research interest, and significant progress has been made in the past decades. However, many attempts to the synthesis of carboranes with more than 14 vertices had been unsuccessful since the report of a 14-vertex carborane in 2005. The question arises as to whether these long sought-after molecules exist. We describe in this article the synthesis and structural characterization of 15- and 16-vertex closo-carboranes as well as 16-vertex ruthenacarborane. Such a success relies on the introduction of silyl groups to both cage carbons, stabilizing the corresponding nido-carborane dianions and promoting the capitation reaction with HBBr2·SMe2. This work would shed some light on the preparation of carboranes with 17 vertices or more, and open the door for studying supercarborane chemistry.

Enantioselective Synthesis of 4-Silyl-1,2,3,4-tetrahydroquinolines via Copper(I) Hydride Catalyzed Asymmetric Hydrosilylation of 1,2-Dihydroquinolines

C–Si bonds were constructed by utilizing copper hydride-catalyzed asymmetric hydrosilylation of 1,2-dihydroquinolines, affording various chiral 4-silyl-1,2,3,4-tetrahydroquinolines in good yields and enantioselectivity. In addition, the C–Si bonds were transformed into C–O bonds with retention of stereochemistry through the Tamao oxidation, giving a series of useful 4-hydroxy-1,2,3,4-tetrahydroquinolines. This method with the enantioselective introduction of silyl groups provides an option to adjust bioactive properties of tetrahydroquinolines.

Semi-bridging σ-silyls as Z-type ligands

The reactions of SiHPh(NCH2PPh2)2C6H4-1,2 with zerovalent group 10 reagents afford the homoleptic bimetallic complexes [M2{μ-κ3-Si,P,P′-SiPh(CH2PPh2)2C6H4}2] (M = Ni, Pd, Pt) in which the M–M bond is unsymmetrically bridged by two σ-silyl groups.

Tuning the stability of alkoxyisopropyl protection groups

Five different 2-alkoxypropan-2-yl groups are introduced as acid-labile protecting groups for the 5’- and 3’-hydroxy groups of a 2’-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % p-toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column chromatography without degradation. The compatibility of these protecting groups in parallel use with benzoyl and silyl groups was verified. The stabilities of the different alkoxy acetal protecting groups were compared by following the kinetics of their hydrolysis at 25.0 °C in buffered solutions through an HPLC method. In the pH range 4.94 to 6.82 the hydrolysis reactions are of first order in the hydronium ion. The rate of hydrolysis correlates with the electron-donating or electron-withdrawing ability of the corresponding alkoxy group. The studied 2-alkoxypropan-2-yl groups and the relative rate constants for their cleavage from the 5’-hydroxy group of 2’-deoxythymidine were: cyclohexyloxy (k rel = 7.7), isopropoxy (7.4), methoxy (1), benzyloxy (0.6) and 2,2,2-trifluoroethyloxy (0.04). The attachment of the same groups to the 3’-hydroxy group are from 1.3 to 1.9-fold more stable. The most reactive of these acetone-based acetal groups are faster removed than a dimethoxytrityl group, and they are easier to cleave completely in solution. The structural variation allows steering of the stability and lipophilicity of the compounds in some range.