In chemistry, solid-phase synthesis is a method in which molecules are bound on a bead and synthesized step-by-step in a reactant solution; compared with normal synthesis in a liquid state, it is easier to remove excess reactant or byproduct from the product. In this method, building blocks are protected by all reactive functional groups and two functional groups in which the reaction occurs between building blocks in the solution and on the bead can be controlled by the order of deprotection. This method is used for the synthesis of peptides, deoxyribonucleic acid (DNA), and other molecules that need to be synthesized in a certain alignment. Recently, this method is also used in combinatorial chemistry.

In the basic method of solid-phase synthesis, building blocks that have two function groups are used. One of the functional groups of the building block is usually protected by a protecting group. The starting material is a bead which binds to the building block. At first, this bead is added into the solution of the protected building block and stirred. After the reaction between the bead and the protected building block is completed, the solution is removed and the bead is washed. Then the protecting group is removed and the above steps are repeated. After all steps are finished, the synthesized compound is cut off from the bead.

If a compound containing more than two kinds of building blocks is synthesized, a step is added before the deprotection of the building block bound to the bead; a functional group which is on the bead and did not react with an added building block has to be protected by another protecting group which is not removed at the deprotective condition of the building block. Byproducts which lack the building block of this step only are prevented by this step. In addition, this step makes it easy to purify the synthesized compound after cleavage from the bead.

Solid-phase synthesis of peptides

Solid-phase synthesis is the most common method for synthesizing peptides. (Peptides are also synthesized with a peptide synthesizer in chemical synthesis.) Usually, peptides are synthesized from the carbonyl group side to amino group side of amino acid in this method, although peptides are synthesized in the opposite direction in cells. In peptide synthesis, amino acid is bound to a bead (resin) at the position of the carbonyl group by using a condensing agent. Then the amino group on the bead is deprotected and reacts with the carbonyl group of the amino acid in a solution in which the amino group is protected. After the reaction, the solution is removed and the bead is washed; the bead bears two amino acids. This cycle is repeated. After all reactions are complete, the synthesized peptide is cleaved from the bead.

The protecting groups for the amino groups mostly used in this peptide synthesis are 9-fuluoromethyloxycarbonyl group (Fmoc) and t-butyloxycarbonyl (Boc). The Fmoc group is removed from the amino group with the base condition while the Boc group is removed with the acid condition.

Solid-phase synthesis of DNA

DNA is also synthesized by the solid-phase method. Although DNA can be synthesized in a flask, it is almost always synthesized by a DNA synthesizer in chemistry. The mechanism of DNA synthesis in a DNA synthesizer is based on solid-phase synthesis; it also uses a bead for synthesis.

See also

• Peptide synthesis.