Scaffold precursors

Spiroproline derivatives are of interest in biological studies as an inhibitor and mechanistic probe of prolyl-4-hydroxylase. To develop potent inhibitors of angiotensinconverting enzyme (ACE), lipophilic and sterically hindered spiroproline derivatives have been substituted in the structural framework of peptides. In addition, spiroprolines could offer interesting scaffold precursors, particularly in synthesis of combinatorial libraries of peptides. Earlier synthetic efforts aimed at spiroproline analogs involved building the proline nucleus on the structural backbone of the alicyclic system followed by resolution. We decided to try to expand the potential of our synthesis of spirocyclic compounds to pro-line derivatives, with the hitherto unknown 2-aza-spiro[4.4]-nonane carboxylic acid (124) derivative as the target. 

With the help of soft chemical synthesis the molecular precursor can be transformed into nanomaterials by retaining the molecular structure intact. The economical feasibility for the synthesis of molecular scaffold precursors was carried out via using a Schelenk type vacuum assembly by taking stringent precautions to avoid moisture. All solvents were dried by standard method [99-100]. 

A series of potent, linear C2-symmetric HIV-1 protease inhibitors with K, values in the nanomolar range was prepared from a diaryl bromide precursor emanating from a carbohydrate scaffold, by application of Heck, Suzuki, Stille, and cyanation reactions. Included in this series was the first reported microwave-promoted Suzuki coupling with an alkyl borane [41]. A very high-yielding Suzuki coupling is presented... 

Some examples of thionocarbamates syntheses on carbohydrate scaffolds from their isothiocyanate precursors were reviewed by Ortiz-Mellet27,28 and more recently by Fernandez-Bolanos.29 The present review will consider the... 

Scheme 1 Sialoside precursors having varied functionalities for direct attachment to hyperbranched or dendritic scaffolds...

In this chapter, we discuss first how the silver clusters relate to silver atoms and silver nanoparticles. Then we overview the formation of fluorescent silver clusters in aqueous solution, using silver salts as precursors and various scaffolds as stabilizers. Finally we discuss applications of silver clusters in fluorescent labeling of biological tissues, and their use as fluorescent probes for sensing of molecules. 

Taru, H., Kirino, Y., Suzuki, T., et al. (2002) Differential roles of JIP scaffold proteins in the modulation of amyloid precursor protein metabohsm. J. Biol. Chem., 277, 21561-2151 A. 

In more recent works, Zhu and coworkers synthesized a variety of para-cyclophanes and biarylether containing macrocycles (14c and d) using a reaction sequence consisting of an Ugi reaction followed by an intramolecular Sj Ar cyclization (Scheme 14) [76-78]. Many linear precursors (14a and b) were achieved with the Ugi reaction by employing varied primary amines. This synthetic planning allowed the introduction of four points of diversity within the resulting scaffolds, thus producing a small library of cyclopeptoids. 

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