Editing Solid-phase synthesis (section)

{{Short description|Method of synthesizing complex molecules}}
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In [[chemistry]], '''solid-phase synthesis''' is a method in which [[molecule]]s are [[Covalent bond|covalently bound]] on a [[solid]] support material and synthesised step-by-step in a single [[reaction vessel]] utilising selective [[protecting group]] chemistry. Benefits compared with normal [[Chemical synthesis|synthesis]] in a [[liquid state]] include:

* High efficiency and throughput
* Increased simplicity and speed

The reaction can be driven to completion and high [[Yield (chemistry)|yields]] through the use of excess [[reagent]]. In this method, building blocks are protected at all reactive [[functional group]]s. The order of functional group reactions can be controlled by the order of deprotection. This method is used for the synthesis of [[peptides]],<ref>{{Cite journal|last=Merrifield|first=Bruce Arthur|date=1963|title=Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide|journal=J. Am. Chem. Soc.|volume=85 |issue=14|pages=2149–2154|doi=10.1021/ja00897a025|bibcode=1963JAChS..85.2149M }}</ref><ref>{{Cite journal|last=Palomo|first=Jose M.|date=2014|title=Solid-phase peptide synthesis: an overview focused on the preparation of biologically relevant peptides|journal=RSC Adv.|language=en|volume=4|issue=62|pages=32658–32672|doi=10.1039/c4ra02458c|bibcode=2014RSCAd...432658P |issn=2046-2069|url=https://digital.csic.es/bitstream/10261/187255/1/Solid-phase_Palomo_Publisher2014.pdf|hdl=10261/187255|hdl-access=free}}</ref> deoxyribonucleic acid ([[DNA]]), ribonucleic acid ([[RNA]]), and other molecules that need to be synthesised in a certain alignment.<ref>{{Cite journal|last1=Krchňák|first1=Viktor|last2=Holladay|first2=Mark W.|date=2002|title=Solid Phase Heterocyclic Chemistry|journal=Chemical Reviews|language=en|volume=102|issue=1|pages=61–92|doi=10.1021/cr010123h|pmid=11782129|issn=0009-2665}}</ref> More recently, this method has also been used in [[combinatorial chemistry]] and other synthetic applications. The process was originally developed in the 1950s and 1960s by [[Robert Bruce Merrifield]] in order to synthesise peptide chains,<ref>{{Cite journal|last=Merrifield|first=B.|date=1986-04-18|title=Solid phase synthesis|journal=Science|language=en|volume=232|issue=4748|pages=341–347|doi=10.1126/science.3961484|issn=0036-8075|pmid=3961484|bibcode=1986Sci...232..341M }}</ref> and which was the basis for his 1984 [[Nobel Prize in Chemistry]].<ref>{{Cite web|url=https://www.nobelprize.org/prizes/chemistry/1984/summary/|title=The Nobel Prize in Chemistry 1984 - NobelPrize.org|website=NobelPrize.org|language=en-US|access-date=2018-09-25}}</ref>

In the basic method of solid-phase synthesis, building blocks that have two functional groups are used. One of the functional groups of the building block is usually protected by a protective 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 synthesised compound is chemically cleaved from the bead.

If a compound containing more than two kinds of building blocks is synthesised, 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 synthesised  compound after cleavage from the bead.