Linkers, photolabile

Photolabile linkers play an important role in solid-phase organic synthesis (SPOS) due to their stability under both acidic and basic conditions. The ONb photolabile linker was modified to improve cleavage rates and yields Fmoc-Tos-OFI was released in 87% yield after 23 h (Scheme 4) [24]. Specifically, the primary alcohol was changed to a secondary benzylic alcohol and the attachment to the resin was through an alkyl chain as opposed to an amide function. Linker 20 was used for the production of carboxylic acids or carbohydrates. A second example... 

Routledge A, Abell C, Balasubramanian S. The use of a dithiane-protected benzoin photolabile safety catch linker for solid-phase synthesis. Tetrahedron Lett 1997 38 1227-1230. 

Peukert S, Giese B. The pivaloyglycol anchor group A new platform for a photolabile linker in solid-phase synthesis. J Org Chem 1998 63 ... 

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. 

Scheme 5.5 Structure and properties of the photolabile linker 17 used for solid-phase synthesis of dodecasaccharide 28.

Several of the phenylene-linked carbenes and nitrenes exhibit photochemical or thermal reactivity in the matrix. The photolabile p- and m-phenylene-linked species give products of rather unexpected structures via mechanisms that are not understood yet. The o-phenylene-linked species isomerize rather easily either via ring opening of the phenylene linker or by an apparent direct reaction of the two proximal diradical centers to give ring-closure products. The available data... 

Schreiber and co-workers (436) prepared a library calculated to contain 2.18 million polycyclic compounds through the 1,3-dipolar cycloaddition of a number of nitrones with alkenes supported on TentaGel S NH2 resin (Scheme 1.83). (—)-Shikimic acid was converted into the polymer bound epoxycyclohexenol carboxylic acid 376 (or its enantiomer), coupled to the resin via a photolabile linker developed by Geysen and co-workers (437) to allow release of the products from the resin in the presence of live cells by ultraviolet (UV)-irradiation. A range of iodoaromatic nitrones (377) was then reacted with the ot,p-unsaturation of the polymer-bound amide in the presence of an organotin catalyst, using the tandem esterification/ dipolar cycloaddition methodology developed by Tamura et al. (84,85) Simultaneous cyclization by PyBrop-mediated condensation of the acid with the alcohol... 

This chemistry was repeated with a traceless photolabile linker.60 The desired biphenyl was formed, but the couplings gave side products, and all yields of the desired biphenyl were lower than 30%. 

An interesting application of the 3-methoxybenzoin-based photolabile linker has been described in which the dithiane, ( )-(3- 2-(l,3-dithian-2-yl)-l-[(9-fluorenylmethoxy-carbonyl)oxy]-2-phenylethyl)benzyl)oxy] acetic acid (126, Scheme 33), a transiently masked form of the caging moiety, is incorporated into a peptide chain generated by solid-phase synthesis. 248 ... 

Photosensitive linkers (see Section 3.1.3) enable the direct analysis of support-bound intermediates by MALDI-TOF MS [14,95,96]. Alternatively, compounds linked to insoluble supports by non-photolabile linkers can be analyzed directly by means of TOF-SIMS [97]. 

Photolabile linkers for amides are most often based on 2-nitrobenzyl derivatives (Table 3.10 for the preparation of these and similar linkers, see also [147,153,235]). The mechanism of photolysis is the same as for the related 2-nitrobenzyl alcohol linkers (Section 3.1.3). 

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 encoding tags are halophenoxy derivatives of aliphatic alcohols and are attached to either a photolabile linker as a carbonate or an oxidatively cleavable linker as an ether. The photolabile linker/tag complex is especially well suited to encode peptide libraries through attachment to approximately 1% of the amino groups of each amino acid synthon at eachstage of the synthesis. For structure determination, the tags are released by photolysis at 360 nM. 

Bochet, C.G. (2002) Photolabile protecting groups and linkers. Journal of the Chemical Society, Perkin Transactions 1, 125-142. 

Cano, M., Ladlow, M. and Balasubramanian, S. (2002) Practical synthesis of a difhiane-protected 3, 5 -dialkoxybenzoin photolabile safety-catch linker for solid-phase organic synthesis. Journal of Organic Chemistry, 67,129-135. 

For the automated synthesis of CS hexasaccharides, Peter Seeberger s group designed a photolabile nitrobenzyl ether-based linker to the Merrifield resin (Scheme 10.15) [31]. Their advanced strategy also differs by the use of monosaccharide donors for the... 

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