Solid-phase synthesis advantages

One widely used method involving protected compounds is solid-phase synthesis (polymer-supponed reagents). This method has the advantage of requiring only a simple workup by filtration such as in automated syntheses, especially of polypeptides, oligonucleotides, and oligosaccharides. 

Soluble support-based synthetic approaches offer the advantages of both homogeneous solution-phase chemistry (high reactivity, ease of analysis) and solid-phase synthesis (large excess of reagents, simple product isolation and purification) [98,99]. As a representative example, PEG, one of the most widely used soluble polymers, has good solubility in most organic solvents (i.e., dichloromethane, acetonitrile, dimethylformamide, and toluene), but it... 

The major requirements for photoactivatable amino acids are that they should exhibit high optical purity and contain appropriate protecting groups for solid-phase synthesis there is also a particular advantage if they contain the radiolabel. While p-azido-phenylalanines can easily be labeled with 125I and... 

Solid-phase synthesis has unique advantages in accommodating purification at each individual reaction step without losing compound mass. However, to ensure reaction completion is a challenging task. Our capability to monitor reactions on... 

The amidoxy, or ip[C0-NH-0], link 6 (R1 = H) results from N-acylation of an a-aminoxy acid. a-Aminoxy acids have been isolated from natural sources and some of them present antibacterial properties as such, or when coupled to an a-amino acid, as in malioxamycin H-L-Vali )[C0-NH-0]D-Asp-0Hj115 117l The a-aminoxy acids are homologous to the a-hy-drazino acids with the advantage that there is no problem of regioselectivity for N-acylation. Despite the easy preparation of a-aminoxy acids,1118-1201 the number of (amidoxy) peptides reported in the literature is rather limited, with no examples of solid-phase synthesis. Recently, it has been observed that the a-aminoxy and a-hydrazino acid units induce quite similar local folded structures.1 21-123 ... 

For the automated solid-phase synthesis of oligonucleotides, however, silica was found to be the support of choice [192-197]. Silica with large pore size (25-300 nm), so-called controlled pore glass (CPG), is generally used for this purpose. The main advantages of CPG, as compared with silica gel, are its more regular particle size and shape, and greater mechanical stability. 

For the solid-phase synthesis of amides, it makes a significant difference whether the amine or the acid is linked to the support. Resin-bound amines are readily acy-lated by adding first a carboxylic acid and then a carbodiimide (Table 13.3). The acid/ carbodiimide ratio is not critical, because both the O-acylisourea (ratio 1 1) and the symmetric anhydride (ratio 2 1) will lead to N-acylation. It should, however, be borne in mind that the half-lives of O-acylisoureas are shorter than those of anhydrides, and for difficult couplings it might be advantageous to acylate with a symmetric anhydride (two equivalents of acid and one of carbodiimide). 

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