Linker sulfur linkers

Figure 7. SEM and XRMA microphotographs of palladium catalysts supported on the amphiphilic resin made by DMAA, MTEA, MBAA (cross-linker) [30]. Microphotographs (a) and (b) show an image and the radial palladium distribution after uptake of [Pd(OAc)2] from water/acetone the precursor diffuses only into the outer layer of the relatively little swollen CFP after reduction the nanoclusters remain close to the edge of the catalyst beads. Microphotographs (c) and (d) show the radial distribution of sulfur and palladium, respectively, after uptake of [PdCU] from water after reduction palladium is homogenously distributed throughout the catalyst particles. This indicates that under these conditions the CFP was swollen enough to allow the metal precursor to readily penetrate the whole of polymeric mass. (Reprinted from Ref. [30], 2005, with permission from Elsevier.)...

Gayo KM, Suto MJ. Traceless linker Oxidative activation and displacement of a sulfur-based linker. Tetrahedron Lett 1997 38 211-214. 

Another sulfur-containing linker was described by Hunt and Roush in 1996 (Scheme 4.6).4... 

Scheme 9.10 Linkers containing sulfur shown with a pentasaccharide and the tetramannoside (the latter before its deprotection).

Linkers based on sulfur, stannane and selenium chemistry are certainly some of the most flexible systems, because these elements can favorably be tailored for the use as fragile points of attachment. 

The development of sulfone linkers, the exploration of sulfone based chemical transformations and cleavage strategies are an important objective in soHd-phase organic synthesis. This kind of Hnker (Tab. 3.7) has been used with thioethers [108], sulfoxides [109], sulfones [110], sulfonic acids and their corresponding derivatives [111]. Because carbon-sulfur bonds can be cleaved under very mild conditions, some Hnkers have been based on this effect. They can be cleaved under reductive conditions ]112, 113], photolytic conditions [114, 115] or with strong bases [116]. Various safety catch Hnkers have been developed based on the fact that thiols can be oxidized to sulfoxides and sulfones [112, 113]. 

Other sulfur linker give alkenes by cleavage with palladium catalyst [206, 207] or heterocycles by cleavage with nucleophiles [208]... 

The stereochemical outcome of such cycloadditions may be altered by substituents attached to the nitrile oxide-olefin linker. Hassner and co-workers (75,240,253-255) and Kurth and co-workers (256) examined the influence of a stereogenic center a to the dipole in the cycloaddition of alkene-tethered nitrile oxides that feature a sulfur or oxygen atom within the connecting chain (Table 6.13). As expected, the diastereofacial selectivity is increased in the presence of fragments with increasing steric demand. Cycloadditions of thioethers show lower... 

In modern medicinal chemistry, the creation of diversity on a structural framework is important. In principle, diversity at positions 2, 4, 6, 7, and 8 of pteridines can be achieved using such solid-phase chemistry. This prototype solid-phase synthesis involved nitrosation of the resin-bound pyrimidine, reduction of nitroso group with sodium dithionite, and subsequent cyclization with biacetyl to afford pteridines 114 and 115. Cleavage from the resin by nucleophilic substitution of the oxidized sulfur linker using w-chloroperbenzoic acid or DMDO led to the pteridine products 116 and 117 (Scheme 23). 

Gayo, L. M. Suto, M. J. Traceless Linker Oxidative Activation and Displacement of a Sulfur-Based Linker, Tetrahedron Lett. 1997, 38, 211. 

The structure of 70 was established by X-ray diffraction analysis (Figure 22). The palladium center is only coordinated by the phosphorus atom of 32 (the sulfur atom remains pendant) and the dvds coligand (r 2 r 2 fashion), resulting in a slightly distorted trigonal planar geometry around the metal. The rigid thioxanthene linker maintains the boron atom remote from the coordination sphere of the metal. 

Ueno et al. also prepared the b i s (2 - n ap h t h y I s u I fe n y 1) - y - CD series in which the naphthyl moieties are very limited in their movement because the linker between naphthalene and CD is only sulfur [37], All isomers of 12(AB), 13(AC), 14(AD), and 15(AE) exhibit only monomer fluorescence due to the rigid linker. It means that the two naphthalene moieties cannot take face-to-face orientation because of the limited flexibility. Although the excimer cannot be used for sensing molecules, Ueno et al. found that the monomer fluorescence intensity increases with increasing guest concentration. Thus, this modified CD series can be used as chemosensors of a different type. 

Fig. 6 The colchicine and vinblastine sites, a Ribbon representation of RB3-SLD and of the two tubulin a 3 heterodimers. The nucleotides (GTP on a, GDP on P), colchicine (Col, yellow) and vinblastine (Vlb, cyan) are shown as ball-and-stick models. The dashed line shows the location of the RB3-SLD linker between the N-terminal cap and the C-terminal helix, which is the least ordered part of RB3-SLD. The sulfur atom of Cys 12 of the P subunit contacting vinblastine is highlighted as a yellow sphere. b,c Illustration of the interfacial interference of destabilizing molecules with MT assembly schematic representation of the (Tc)2R-vinblastine complex (b) and of a straight protofilament (c). Longitudinal MT-specific contacts (black rectangles in c) cannot be established between vinblastine- or colchicine-bound monomers...

Because of an increased demand for flexible anchoring of molecules, other new families of linkers such as the sulfur linkers and triazene linkers have emerged. The most abundant type of linkers developed so far are based on benzylic-type groups. 

Sulfur has been used in linkers such as thioethers, sulfoxides, sulfones, sulfonic acids and their corresponding derivatives. A safety-catch linker for amines is based on 2-(thiobenzyl)ethylcarbamates [44]. Linkage is performed with preformed handles containing ethenyloxycarbonyl-protected amines 37. Attachment to thiomethyl-ated polystyrene 38 is performed under conditions involving radicals. Cleavage was performed with an oxidizing agent, which forms the retro Michael substrate (Scheme 6.1.11). 

Cleavage reagents Benzyl- type linkers Ketal/ acetal linkers Esters/ amide linkers Silyl linkers Triazene linkers Selenium/ sulfur/ stannane linkers... 

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