Benzoin linker

In order to avoide premature photolysis of the benzoin linker by adventitious room light during the course of the synthesis, the dithiane-protected 3-alkoxybenzoin (49a) has been suggested as a UV-inactive linker. The dithiane-protected 3-alkoxybenzoin (49a) released less than 3% of the product after irradiation at 350 nm. The photosensitivity is restored by hydrolysis of the dithiane prior to photocleavage, as illustrated in Eq. (69.22). Photolysis of the deprotected linker resulted in a 75% yield of the product... 

Poly(acrylic acid) and Poly(methacrylic acid). Poly(acryHc acid) (8) (PAA) may be prepared by polymerization of the monomer with conventional free-radical initiators using the monomer either undiluted (36) (with cross-linker for superadsorber appHcations) or in aqueous solution. Photochemical polymerization (sensitized by benzoin) of methyl acrylate in ethanol solution at —78° C provides a syndiotactic form (37) that can be hydrolyzed to syndiotactic PAA. From academic studies, alkaline hydrolysis of the methyl ester requires a lower time than acid hydrolysis of the polymeric ester, and can lead to oxidative degradation of the polymer (38). Po1y(meth acrylic acid) (PMAA) (9) is prepared only by the direct polymerization of the acid monomer it is not readily obtained by the hydrolysis of methyl methacrylate. 

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. 

The development of light-sensitive protective groups began in the early 1960s [129-131] and led to the identification of several functionalities that could be selectively cleaved under UV irradiation (for a review, see [132]). Some of these protective groups, such as 2-nitrobenzyl esters, carbonates, or carbamates [131,133-135], benzoin [136-139], and other phenacyl esters [140] were also found to be useful as photocleavable linkers. 

Most photocleavable linkers for carboxylic acids used today are based on the photoisomerization of 2-nitrobenzyl esters and on the light-induced cleavage of phen-acyl esters (Figure 3.10). Several possible mechanisms have been proposed for the photolytic cleavage of benzoin esters. One of the most recent is the dissociation of the excited phenacyl ester into a carboxylate and a phenacyl cation ( photosolvolysis , Figure 3.10 [136]). 

Poly(acrylic acid) and Poly(rnethacrylic acid). Poly(acrylic acid) (PAA) may be prepared by polymerization of the monomer with conventional free-radical initiators using the monomer either undiluted (widi cross-linker for superadsorber applications) or in aqueous solution. Photochemical polymerization (sensitized by benzoin) of methyl acrylate in ethanol solution at —78°C provides a syndiotactic form that can be hydrolyzed to syndiotactic PAA. 

A further safety-catch linker is based on a difhiane-protected benzoin (173). It can be activated for cleavage by photolysis according to Scheme 79, after removal of the dithiane protection [194]. It can be applied to the attachment and subsequent release of alcohols and carboxylic acids. A disadvantage is that if activation is performed with a Hg(II) salt, then this must be removed completely in order to avoid problems in assays using proteins as biological targets. 

Routl997a Routledge, A., Abell, C. and Balasubramanian, S., The Use of a Dithiane Protected Benzoin Photolabile Safety Catch Linker for Solid-Phase Synthesis, Tetrahedron Lett., 38 (1997) 1227-1230. 

There are a number of examples of benzoin and substituted benzoin esters that have been employed as photoremovable protecting groups for carboxylic acids. Among these, the application of benzoin as a traceless linker for solid-phase synthesis of oligopeptides and introduction of Fmoc-protected amino acids by Balasubramanian ° is instructive. As an example, the release of Fmoc-Ala shown in Eq. 69.21 occurs upon photolysis at 350. Balasubramanian found that the maximum yield was obtained after a 2-h photolysis as determined by HPLC (Eq. (69.21). 

---