Editing Aspartame (section)

==Chemistry==

Aspartame is a [[methyl ester]] of the [[dipeptide]] of the natural [[amino acid]]s <small>L</small>-[[aspartic acid]] and <small>L</small>-[[phenylalanine]].<ref name=pubch/> Under strongly [[acid]]ic or [[Base (chemistry)|alkaline]] conditions, aspartame may generate [[methanol]] by [[hydrolysis]]. Under more severe conditions, the [[peptide bond]]s are also hydrolyzed, resulting in free amino acids.<ref>
{{Cite journal| vauthors = Ager DJ, Pantaleone DP, Henderson SA, Katritzky AR, Prakash I, Walters DE | title = Commercial, Synthetic Non-nutritive Sweeteners| journal = [[Angewandte Chemie International Edition]]| year = 1998| volume = 37| issue = 13–24| pages = 1802–8117| doi = 10.1002/(SICI)1521-3773(19980803)37:13/14<1802::AID-ANIE1802>3.0.CO;2-9 }}</ref>

[[File:Beta aspartame.png|thumb|right|alt= Beta aspartame differs from aspartame based on which carboxyl group binds to phenylalanine|Beta-aspartame differs from aspartame based upon which carboxyl group of aspartate binds to the nitrogen of phenylalanine.]]

Two approaches to synthesis are used commercially. In the chemical synthesis, the two carboxyl groups of aspartic acid are joined into an anhydride, and the amino group is [[Protecting group|protected]] with a [[formyl group]] as the formamide, by treatment of aspartic acid with a mixture of formic acid and acetic anhydride.<ref>{{Cite patent|title=Process for producing N-formylamino acid and use thereof|country=US|number=20040137559|issue-date=2003-10-20}}</ref> Phenylalanine is converted to its methyl ester and combined with the ''N''-formyl aspartic anhydride; then the protecting group is removed from aspartic nitrogen by acid hydrolysis. The drawback of this technique is that a byproduct, the bitter-tasting β-form, is produced when the wrong carboxyl group from aspartic acid anhydride links to phenylalanine, with desired and undesired isomer forming in a 4:1 ratio.<ref>{{cite web|url=https://www.chemistryviews.org/details/ezine/9138171/The_Saccharin_Saga__Part_6.html|title=The Saccharin Saga – Part 6|work=ChemViews Magazine|date=5 April 2016|access-date=18 March 2019|archive-date=2 June 2018|archive-url=https://web.archive.org/web/20180602151924/http://www.chemistryviews.org/details/ezine/9138171/The_Saccharin_Saga__Part_6.html|url-status=live}}</ref> A process using an [[Thermolysin|enzyme from ''Bacillus thermoproteolyticus'']] to catalyze the condensation of the chemically altered amino acids will produce high yields without the β-form byproduct. A variant of this method, which has not been used commercially, uses unmodified aspartic acid but produces low yields. Methods for directly producing aspartyl-phenylalanine by enzymatic means, followed by chemical methylation, have also been tried but not scaled for industrial production.<ref>{{cite journal | vauthors = Yagasaki M, Hashimoto S | title = Synthesis and application of dipeptides; current status and perspectives | journal = Applied Microbiology and Biotechnology | volume = 81 | issue = 1 | pages = 13–22 | date = November 2008 | pmid = 18795289 | doi = 10.1007/s00253-008-1590-3 | s2cid = 10200090 }}</ref>