O-nitrobenzyl derivatives

Even though most commonly used photoremovable protecting groups in applications are based on o-nitrobenzyl derivatives, the mechanistic details of photorelease from nitrobenzyl derivatives were not known. Recently, Wirz et al. and Corrie et al. investigated the mechanism. The mechanism of photorelease from the photo-enols formed by irradiating 2-nitrobenzoyl compounds is more complex than for o-alkyl arylketones. 

Photolysis of o-Nitrobenzyl Derivatives - The cleavage of o-nitrobenzyl derivatives is one of the relatively few classes of photofragmentations in which the two fragments can both bear complex functionality. The protection of alcohols as o-nitrobenzyl ethers is well known, and provides a photochemical method of deprotection, but other applications include the design of photoclea-vable polymers and photochemically active links for molecules synthesized on polymer beads. 

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. 

The fj-nitrobenzyl and p-nitrobenzyl ethers can be prepared and cleaved by many of the methods described for benzyl ethers. In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate 280 nm, 95% yield of nucleotide ). This is one of the most important methods for cleavage of this ether. These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative." Clean reduction to the aniline is accomplished with Zn(Cu) (acetylacetone, rt, >93% yield).Hydrogenolysis is also an effective means for cleavage. A polymeric version of the o-nitrobenzyl ether has been prepared for oligosaccharide synthesis that is also conveniently cleaved by photolysis. An unusual selective deprotection of a bis-o-nitrobenzyl ether has been observed. The photochemical reaction of o-nitrobenzyl derivatives has been reviewed. ... 

Photorearrangement of o-nitrobenzyl derivatives is a well-established process and proceeds via intramolecular hydrogen abstraction. A pathway of this type is initially involved in the conversion of the 1-(o-nitrobenzyl)-2-acylpyrazolidin-3-ones (70) into the 1-(acylamino)azetidin-2-ones (71) as shown in Scheme 4, ... 

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. 

Photolysis of o-Nitrobenzyl Derivatives and Related Compounds. - Time-resolved FTIR monitoring of the flash photolysis of several l-(2-nitrophe-nyl)ethyl ethers (83) (Scheme 15) have shown that two parallel pathways are involved, but that release of the alcohol (89) is rate-limited by the decomposition of a common hemiacetal intermediate (88). " The two pathways are... 

Fig. 2. Photocleavage of o-nitrobenzyl derivatives of amino acids and peptides 236...

Walker, J. W., McCray, J. A. Hess, G. P. (1986). Photolabile protecting groups for an acetylcholine receptor ligand. Synthesis and photochemistry of a new class of o-nitrobenzyl derivatives and their effects on receptor function. Biochemistry, 25, 1799-805. 

The photolabile o-nitrobenzyl derivative was utilized to protect the phenolic OH group of serotonin. The serotonin type-3 receptor is the only ligand-gated ion channel in the 5-HT receptor family. The protection of the phenolic hydroxy group of serotonin required four steps, as shown in Scheme 13. The substrate was released upon excitation with 337-nm laser pulses. The signal decay from pulsed laser... 

Protection of Hydroxyl Groups. Photolabile 2 -0-(o-nitrobenzyl) derivatives of various ribonucleotides as well as dinucleotides have been synthesized, and their subsequent photodeprotections, which yield the corresponding alcohols, examined (eq 11). Protection of the anomeric hydroxyl functionality of 2-deoxy-D-ribofuranose has been accomplished using o-NBA (eq 12). This protective group is quite stable to acidic conditions, and has proven invaluable in the synthesis of abasic oligonucleotides. Similar conditions are employed in the synthesis of bis(o-nitrobenzyl) ethers. ... 

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