O-nitrobenzyl linkers

A different, pivaloylglycol-based photolabile hnker 1.26 (83) was prepared with a complex, eight-step procedure from dihydroxyacetone dimer and aminomethyl Ten-tagel resin the linker was used to support and to further elaborate carboxylic acids. The photolytic release at 320 nm of elaborated acids compared favorably with more assessed o-nitrobenzyl linkers. 

Fraser-Reid and co-workers designed a photolabile o-nitrobenzylic linker 268, which was used in the synthesis of a branched trimannan oligosaccharide 271 (O Scheme 41) [139]. Differentially protected NPG 269 was coupled to the resin via linker 268. Selective removal of the C6 chloroacetyl and C3 acetyl groups, followed each by mannosylation (NIS/TESOTf) with NPG 64, afforded trimannan 271, in 42% overall yield after photolytic cleavage. 

In a related approach, Fraser-Reid and co-workers used Chiron s polystyrene-grafted crowns with Rich s photocleavable o-nitrobenzyl linker [140] and NPG donors in the synthesis of trisaccharide 277 (O Scheme 42) [141]. After attachment of the first aminoglucosyl moiety to... 

Holmes [25] prepared a series of known nitrobenzyl-derived photolabile linkers and examined their rates of photolytic cleavage in various solvents (Table 17.3). When irradiated at 365 nm, o-nitrobenzyl linker 13 showed the slowest rate of cleavage in all solvents a-methyl substituted linkers (15-17) were also cleaved faster than the non-substituted linker 14 in all solvents. Increasing the length of tether (16) between the resin and linker slightly improved reaction rates in organic solvents, but diminished them in aqueous buffer. 

Comparison of o-Nitrobenzyl Linkers 476 17.2.2 Functionalized Phenylacyl Linkers 477... 

In polymer 35 two polystyrene (PS) and PEO blocks were connected with the photolabile o-nitrobenzyl linker. Light exposure cleaved the polymer backbone and separated the hydrophobic and hydrophiUc blocks. This process was successfully carried out in solution and also in solid state. Thin films of polymer 35, annealed to obtain the vertically aligned cylindrical morphology, were exposed and washed with methanol/water after irradiation. A nanoporous PS film was obtained. This kind of diblock copolymer... 

A catch and release system based on a strained allqme constmct has been studied and is thought to be well suited for proteomics applications. This is based on a photolable o-nitrobenzyl linker/cyclooctine conjugate. ... 

Holmes CP, Jones DG. Reagents for combinatorial organic synthesis Development of a new o-nitrobenzyl photolabile linker for solid-phase synthesis. J Org Chem 1995 60 2318-2319. 

Many other linkers besides those listed above have been developed for two-phase synthesis of oligosaccharides on insoluble supports, and it can be expected that at least some of them will be tested on soluble supports. It should be kept in mind that MPEG-supported syntheses can be easily scaled up therefore, any relationship between both types of polymer supports will be cooperative rather than mutually exclusive. Such linkers will most probably include dialkyl- or diaryl-silyl linkers,10,41 3 and linkers cleavable by photolysis such as the o-nitrobenzyl group and its modifications.44 16... 

A class of photolabile linkers has been developed to circumvent the use of silyl ethers as linkers and allow for the use of temporary silyl protecting groups.34,35 Photolabile linkers, such as 2, often involve the use of o-nitrobenzyl ether groups. This functional group is stable to a variety of conditions however, cleavage from the polymer support is often slow and... 

The original o-nitrobenzyl bromide linker 1.19 (76) attached to aminomethyl PS resin has been used for both peptide and small organic molecule SPS. Cleavage by photolysis at 350 nm under anaerobic conditions gives carboxylic acids the insertion of an a-methyl allowed an easier cleavage (77). The linker 1.19 has also been prepared... 

Another aminomethyl PS resin supported o-nitrobenzyl photolabile hnker 1.23 (80) has been employed for the synthesis of heterocycles such as thiazohdinones. Attachment to the resin is through an acid or aldehyde group and photolytic cleavage is performed in 5% dimethyl sulfoxide (DMSO)-aqueous buffer to facilitate the biological testing of the final compound. A photolabile hydroxyl linker 1.24 (81), again supported on aminomethyl PS resin, has been used to synthesize carbohydrate and peptide derivatives in SP. The easily prepared diol linker 1.25 (82) allowed the attachment of aldehydes as acetals and their photo induced release using standard conditions. 

Rodebaugh R, Fraser-Reid B, Geysen HM. A new o-nitrobenzyl photocleavable linker for solid phase synthesis. Tetrahedron Lett. 1997 38 7653-7656. 

Holmes, C.P. Model Studies for New o-Nitrobenzyl Phololabile Linkers Substituent Effects on the Rates of Photochemical Cleavage, J. Org. Chem. 62, 2370-2380 (1997). 

Holmes, C.P Jones, D.G. Reagents for Combinatorial Organic Synthesis Development of a New o-Nitrobenzyl Photolabile Linker for Solid Phase Synthesis, ... 

For application in combinatorial synthesis, photolabile linkers must be modified to allow for attachment to the solid support, and must be further modified to adjust the cleavage step after combinatorial synthesis to the requirements of the photo-lytic removal of the target molecules from the support (modulation of photolytic cleavage kinetics). For combinatorial synthesis, only the o-nitrobenzyl-derived linkers have found wide application, while the Desyl-derived linker has been used mostly in photolithographic DNA synthesis. 

Various o-nitrobenzyl-based linkers are outlined in Fig. 14, together with the acyl... 

Scheme 6.192 shows the o-nitrobenzyl moiety used as a photolabile linker in the solid-phase oligosaccharide synthesis on a polystyrene (PS) support.1208 After the synthesis of the protected oligosaccharide 404, PS attached to the photoremovable group is removed by photolysis and the final product is obtained by hydrogenolysis. Such a strategy could be promising for combinatorial synthesis of oligosaccharide libraries. 

Photolysis of o-Nitrobenzyl Derivatives and Related Compounds. - Although novel types of photolabile protecting groups are continually being developed, the 2-nitrobenzyl system remains popular, especially for photocleav-able linkers in solid-state synthesis or for the photo-induced released of so-called caged molecules. In the period under review, there were few mechanistic studies of the photolysis of 2-nitrobenzyl derivatives, but some significant applications were described. 

Novel photocleavable, o-nitrobenzyl based linkers for solid-phase synthesis have been developed and 7V-(2-nitrobenzyloxycarbonyl) cyclic amines have been synthesized as photobase generating agents for resists. ... 

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