Tether stable

As an extension to thep-carboxybenzenesulfonamide safety-catch linker [43,44], alkanesulfonamide handle 37 was developed [45]. This linker tethers carboxylic acids to the solid support to give an acylated sulfonamide which is stable to both basic and acidic conditions (Scheme 12). Products were released by treatment with iodoacetonitrile followed by the addition of a nucleophile. 

The base lability of succinoyl diester hnker severely limits the selection of protecting groups available for an oligosaccharide synthesis, so a more versatile tether was required. Diether bonds of benzylphenol or dibenzyl of 1,4-di(hydroxymethyl)-benzene satisfy this requirement because they are stable to both bases and to acids. A sufficient acid stability is important since the formation of a glycosidic bond is an acid-catalyzed reaction, not surprisingly, as it is an acetal functionality. For instance, DOX,34 the dibenzyl hnker a,a -DiOxyXylyl diether, -0CH2C6H4CH20-, is not limited by restriction of the succinoyl hnker (1) when bound via a hydroxyl or as an... 

A key aspect of any synthesis strategy on a polymeric support is the linkage element, which acts as a tether to the polymeric support. Ideally, the linker should be stable to all reaction conditions used in a synthesis sequence and should be cleaved quantitatively under conditions that do not degrade the desired target molecule [6]. In this overview the different kinds of linkers and the synthetic transformations that can be used on polymeric supports will be presented. At the end, synthetic strategies for the synthesis of heterocycles and natural products will be mentioned. 

The reaction of 1,4-diphenylbuta-l,3-diene (2) with trithiazyl trichloride (3) yields a bi(thiadiazole) (4), an isothiazoloisothiazole (5), a dithiazolothiazine (6), and two thiazin-odithiatriazepines (7) and (8) by 1,2-, 1,3-, and 1,4-cycloaddition reactions (Scheme 2). The bridged-mode (/3-tether) tandem inter-[4 -E 2]/intra-[3 -E 2] cycloaddition of (ii)-2-methyl-2-nitrostyrene (9) with 1-butoxypenta-1,4-diene (10) produces stable tricyclic nitroso acetals (11) which afford, after reduction and protection, highly functionalized aminocyclopentanedimethanol triacetates (12) (Scheme 3). ... 

By contrast, in 2000 Shibata reported the Ir-catalyzed enantioselective Pauson-Khand-type reaction of enynes [30aj. The chiral Ir catalyst was readily prepared in situ from [lrCl(cod)]2 and tolBINAP (2,2 -bis(di-p-tolylphosphino)-l,T-binaphthyl), both of which are commercially available and air-stable, and the reaction proceeded under an atmospheric pressure of carbon monoxide. The Ir-catalyzed carbonylative coupling had a wide generality in enynes with various tethers (Z), substituents on the alkyne terminus (R ) and the olefinic moiety (R ). In the case of less-reactive enynes, a lower partial pressure of carbon monoxide achieved a higher yield and ee-value (Table 11.1) [30b]. 

As illustrated above, peptides have been used as tethering elements for the suitable positioning of carbohydrate moieties. Since the chemistry of glycopeptides is well under control, the approach may appear valuable, at least a priori. This is likely to be true for research investigations. However, as neoglycopeptides should eventually developed into useful therapeutics, the synthesis of novel and metabolically stable neoglycopeptidomitics was undertaken [110-113]. The approach chosen was commensurate to that used for the synthesis of peptoids. 

Figure 8.5 Interaction potential for model whey protein layer consisting of densely packed brush-like tethered chains with small a fraction of the whev protein replaced by p-casein chains as represented by a copolymer model. The energy A d) calculated from SCF theory is plotted as a function of surface-surface separation d A, no p-casein B, 2.5% p-casein C, 5% p-casein D, 5% p-casein alone (without whey protein layer). Potentials A, B and D imply that the emulsion system is flocculated potential C implies a stable emulsion state. Reproduced from Dickinson (2006b) with permission.

The first detailed study of the individual steps of the cationic pathway of the intramolecular Heck reaction was recently described by Brown (Scheme 8G.21) [46], Oxidative addition of aryl iodide 21.1 to [l,l -bis(diphenylphosphino)ferrocene](cyclooctatetraene)palladium generated 21,2. Complex 21.2 was stable at room temperature and was characterized by X-ray crystallography no interaction between the palladium center and the tethered alkene was observed in this intermediate. Treatment of 21.2 with AgOTf at -78°C removed iodide from the palladium coordination sphere, which facilitated a rapid alkene coordination and subsequent... 

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