Linker methodology

Wu, X. Y. Btmdle, D. R., Synthesis of glycoconjugate vaccines for Candida albicans using novel linker methodology. J. Org. Chem. 2005,70, 7381-7388. 

Zhao XY, Jung KW, Janda KD, Soluble polymer synthesis an improved traceless linker methodology for aliphatic C-H bond formation, Tetrahedron Lett., 38 977-980, 1997. 

Liebe and Kunz made further use of the HYCRON linker methodology in the construction of the a2-6 sialyl-TN antigen attached to a portion of the mucin MUCl repeat peptide [104] (O Scheme 20). 

Key words bond forming reactions, function group conversion, heterocyclic synthesis, linker methodology, solid phase synthesis... 

R. Roy, M. Corazon Trono, and D. Giguere, Effects of linker rigidity and orientation of mannoside clusters for multivalent interactions with proteins, in R. Roy, (Ed), Glycomimetics Modern Synthetic Methodologies, ACS Symp. Ser., 896 (2005) 137-150. 

The chapter focuses more on describing the general approaches to ion-radical syntheses and synthetic methodology, than providing a detailed account of each reaction. The examples chosen is aimed at illustrating the usefulness of the ion-radical reactions by providing preparative applications (see also some preceding sources — Linker and Schmittel 1998 and Little and Moeller 2002). 

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... 

An exception to this was a report in 2003 by Seeberger and co-workers, where catalyst 6 was found to cleave the octenediol linker of an azide-containing sugar in high yield (Scheme 16). Use of 1-pentene as a cross-partner in place of ethylene proved crucial to attaining high reaction yields. This methodology was later successfully adapted to solid-phase synthesis. 

The still modest yield (8%) obtained with the hexamethylene linker being far from satisfactory, we explored various other possibilities. Among them a 1,3-phe-nylene spacer, already used with success by others in the construction of helical complexes [99-101], seemed very appealing owing to its expected chemical robustness (necessary to survive the harsh cyclization conditions) and ease of introduction following our methodology [95]. 

---