Solid phase synthesis strategy for

Liu, G. Ellman, J. A. A General Solid-Phase Synthesis Strategy for the Preparation of 2-Pyrrolidinemethanol Ligand, J. Org. Chem. 1995,60, 7712. 

SCHEME 8.3 Solid-phase synthesis strategy for introducing diversity at the C-3 and C-2 positions of a disaccharide template. 

Eda and Kurth applied a similar solid-phase combinatorial strategy for synthesis of pyridinium, tetrahydropyridine, and piperidine frameworks as potential inhibitors of vesicular acetylcholine transporter. One member of the small library produced was prepared from amino-functionalized trityl resin reacting with a 4-phenyl Zincke salt to give resin-bound product 62 (Scheme 8.4.21). After ion exchange and cleavage from the resin, pyridinium 63 was isolated. Alternatively, borohydride reduction of 62 led to the 1,2,3,6-tetrahydropyridine 64, which could be hydrogenated to the corresponding piperidine 65. 

SCHEME 52. Solid-phase synthetic strategy for 1,4-benzodiazepine derivatives using a germanium linker strategy i) polymer support linkage, ii) solid-phase synthesis, iii) product release... 

The synthesis reported by Hamacher et al. has been routinely used to prepare [ F]FDG in PET production centers around the world. The synthesis requires no HPLC purification, and the described RCY was excellent (>90%, EOB). As noted above, [ F]FDG is the most widely used fluorine-18-labeled radiopharmaceutical to date, and so the synthesis has also been adapted for solid phase. SPOR strategies for preparation of [ F]FDG, shown in Scheme 13.3, have beenreportedby Wadsworth etal. and Brady etal. and illustrate proof-of-concept. Notably, these authors used a concept based on perfluorosulfonate linker units to attach the precursor to the resin. The cleavage step used standard radiofluorination... 

Jensen KJ, Alsina J, Songster MF, Vagner J, Albericio F, Barany G. Backbone amide linker (BAL) strategy for solid-phase synthesis of C-terminal-modified and cyclic peptides. J Am Chem Soc 1998 120 5441— 5452. 

Ellman JA, Plunkett MJ. Germanium and silicon linking strategies for traceless solid-phase synthesis. J Org Chem 1997 62 2885-2893. 

Allylic amination is important for the solid-phase organic synthesis.15 The solid-phase allylic aminations are devised into the G-N bond formation on solid support and the deprotection of allyl ethers. As a novel deprotection method, the palladium-catalyzed cyclization-cleavage strategy was reported by Brown et al. (Equation (4)).15a,15b The solid-phase synthesis of several pyrrolidines 70 was achieved by using palladium-catalyzed nucleophilic cleavage of allylic linkages of 69. 

In summary, we have described an efficient and facile solid-phase synthesis of substituted ureas starting from aminomethyl MicroTubes. The synthesis takes place under mild conditions. Taking into account the commercial availability of primary amines, this strategy can be ideally used for the synthesis of large combinatorial libraries. 

BACKBONE AMIDE LINKER (BAL) STRATEGY FOR SOLID-PHASE SYNTHESIS... 

Solid-phase synthesis of biomolecules, of which peptides are the prime example, is well established. The search for more effective therapeutic agents creates a need for different strategies to synthesize peptides with C-terminal end groups other than the usual carboxylic acid and carboxamide functionalities. Methods described herein are readily generalized to small nitrogen-containing organic molecules. 

In conclusion, the BAL method is a novel and general strategy for solid-phase synthesis of peptides and peptide derivatives, is compatible with a wide range of functionalized polymeric supports, and is readily generalizable to other nitrogen-containing molecules.9... 

---