Synthetic scaffolds

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

Fig. 14 Use of two different DNA duplexes with inserted cytosine loops working as synthetic scaffolds to generate fluorescent silver clusters for the identification of the sickle cell anemia gene mutation (black dots represent hydrogen bonds formed in base pairing and black dashed lines the sugar-phosphate backbone) [74]...

C60 is also a highly versatile synthetic scaffold that can easily be functionalized by the methods of synthetic organic chemistry. The formation of C60 derivatives (i.e., covalently modified C60) nearly always involves the addition of a functional group (addend) across one or more of its 30 double bonds. When only one addend is attached, the fullerene derivative is called a monoadduct, with two, a bisadduct, etc. The ability to sensitize molecular oxygen in the presence of visible light is retained in the simple derivatives of C60 (i.e., mono-, bis-, and trisadducts). 

On the nanoscale, the surface chemistry of the scaffold must recreate the important cell-ECM properties of adhesion and control. Biocompatibility of the scaffold surface with cells is key for allowing adhesion and migration of cells. The amino acid sequence of arginine-glycine-aspartic acid (RGD) has been identified on fibronectin and other ECM glycoproteins as a key adhesion domain, and the design of synthetic scaffolds incorporating the peptide has been successful... 

Currently, two strategies have emerged as the most promising tissue engineering approaches [53]. One is to implant pre-cultured cells and synthetic scaffold... 

Rational inhibitor design offers a compelling alternative for the identification of protein-protein disrupters as it is based on a structural knowledge of the interface. In particular, synthetic scaffolds that mimic the key elements of a protein surface can potentially lead to small molecules with the full activity of a protein domain, a fraction of the molecular weight, and no peptide bonds. Furthermore, lead compounds derived from rational design can be readily optimized by structure-activity relationship (SAR) studies. 

Kharande TS, Agrawal CM (2008) Functions and requirements of synthetic scaffolds in tissue engineering. In Laurencin CT, Nair LS (eds) Nanotechnology and tissue engineering the scaffold. CRC, Boca Raton... 

A.J. Campillo-Fernandez, R.E. Unger, K. Peters, S. Halstenberg, M. Santos, M. Salmeron Sanchez, et al.. Analysis of the biological response of endothelial and fibroblast cells cultured on synthetic scaffolds with various hydrophilic/hydrophobic ratios influence of fibronectin adsorption and conformation. Tissue Eng. Part A 15 (2009)1331-1341. 

In such temporary functional scaffoldings, natural cells can be induced into the scaffold, attached, and stretched due to the pulsing blood as a consequence, cells remodel the synthetic scaffold into a natural tissue sufficient to sustain essential mechanical function. 

Fig. 5 Desired Properties of an Ideal Synthetic Scaffold. From Murugan R, Kumar TSS, Ramakrishna S. Scaffolds for bone tissue restoration from biological apatite. Trends Biomater. Artif. Organs. 2006 20 35-39.

Acetates 2 are reactive intermediates that can be used in iS n2 substitution reactions with C-, N-, 0-, S- and P-nucleophiles, leading to multi-substituted alkenes as advanced synthetic scaffolds (Section 3.8). 

Preliminary investigations of the reactivities of these unusual, strained heterocyclic compounds (513) have demonstrated their potential as synthetic scaffolds. The conversion of electron-rich 3-aryl-2-methylene-3-hydroxy acids 511 into electron-rich aryl allenes 514 at room-temperature is an unanticipated transformation that may have synthetic utility. ... 

Moreover, the methylenation of lactones 210 with dimethyltitanocene was examined to synthesize 3-alkylidene-2-methyleneoxetanes 212. The yields of 212 depended strongly on the steric hindrance at C4. Bulkier substituents at C4 led to higher yields, and up to 75% yield was acquired with lactones 210d. Preliminary investigations of the reactivity of these unusual, strained hetero-cycUc compounds have been carried out. Using 212a as a model substrate, several potential applications of such 3-alkylidene-2-methyleneoxetanes as synthetic scaffolds were demonstrated (Scheme 4.64). 

Common synthetic scaffolds in the synthesis ofstmcturaUy diverse natural products 12CSR5613. 

The Robinson-Schdpf condensation has been employed to construct structures other than the familiar tricyclic core. In addition, there are cases where once obtained, the triyclic core is fragmented into natural or synthetic scaffolds. Contexts for use of the Robinson-Schopf in these ways include hydroazulenes," betalains, ( )-coniine, pyrrolidine synthons, " and substituted piperidones. ... 

Synthetic scaffolds inspired by nature are used to improve the overall biological pathway performance. Chemical methods are exploited enabling the covalent linkage of a set of enzymes to the same macromolecular scaffold and modular processes (enzymes distributed in different reactors) are an alternative to overcome the limitations of one-pot processes. 

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