Editing Strychnine (section)

== Chemical synthesis ==
{{Main|Strychnine total synthesis}}

As early researchers noted, the strychnine molecular structure, with its specific array of [[Ring (chemistry)|rings]], [[stereocenter]]s, and nitrogen [[functional group]]s, is a complex synthetic target, and has stimulated interest for that reason and for interest in the [[structure–activity relationship]]s underlying its pharmacologic activities.<ref>{{cite journal | vauthors = Nicolaou KC, Vourloumis D, Winssinger N, Baran PS | title = The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century | journal = Angewandte Chemie | volume = 39 | issue = 1 | pages = 44–122 | date = January 2000 | pmid = 10649349 | doi = 10.1002/(SICI)1521-3773(20000103)39:1<44::AID-ANIE44>3.0.CO;2-L | s2cid = 20559096}}</ref> An early synthetic chemist targeting strychnine, [[Robert Burns Woodward]], quoted the chemist who determined its structure through chemical decomposition and related physical studies as saying that "for its molecular size it is the most complex organic substance known" (attributed to [[Robert Robinson (organic chemist)|Sir Robert Robinson]]).<ref>{{cite journal | vauthors = Robinson R | year = 1952 | title = Molecular structure of Strychnine, Brucine and Vomicine | journal = Progress in Organic Chemistry | volume = 1 | pages = 2}}</ref><ref>{{cite journal | vauthors = Seeman JI, House MC | author-link1 = Jeffrey I. Seeman | year = 2022 | title = 'For Its Size, the Most Complex Natural Product Known.' Who Deserves Credit for Determining the Structure of Strychnine? | journal = [[ACS Central Science]] | volume = 8 | issue = 6 | pages = 672–681 | doi = 10.1021/acscentsci.1c01348 | pmc = 9228570 | pmid = 35756373 | quote = For its molecular size it is the most complex substance known.}} citing {{cite journal | vauthors = Woodward RB, Cava MP, Ollis WD, Hunger A, Daeniker HU, Schenker K | year = 1963 | title = The Total Synthesis of Strychnine | journal = [[Tetrahedron (journal)|Tetrahedron]] | volume = 19 | issue = 2 | pages = 247–288 | doi = 10.1016/S0040-4020(01)98529-1}}</ref>

[[File:Strychnine Star chemdraw.jpg|class=skin-invert-image|300px|left]]

The first [[total synthesis]] of strychnine was reported by the research group of R. B. Woodward in 1954, and is considered a classic in this field.<ref>{{cite book | vauthors = Nicolaou KC, Sorensen EJ | date = 1996 | title = Classics in Total Synthesis: Targets, Strategies, Methods | publisher = Wiley | isbn = 978-3-527-29231-8}} {{page needed|date=June 2014}}</ref><ref name="Bonjoch 3455–3482" /> The Woodward account published in 1954 was very brief (3 pages),<ref>{{cite journal | vauthors = Woodward RB, Cava MP, Ollis WD, Hunger A, Daeniker HU, Schenker K | title = The total synthesis of strychnine | journal = Journal of the American Chemical Society | volume = 76 | issue = 18 | pages = 4749–4751 | year = 1954 | doi = 10.1021/ja01647a088| bibcode = 1954JAChS..76.4749W }}</ref> but was followed by a 42-page report in 1963.<ref>{{cite journal | vauthors = Woodward RB | title = The total synthesis of strychnine | journal = Experientia | volume = 19 | issue = Suppl 2 | pages = 213–228 | year = 1963 | pmid = 13305562 | doi = 10.1016/S0040-4020(01)98529-1}}</ref> The molecule has since received continuing wide attention in the years since for the challenges to synthetic organic strategy and tactics presented by its complexity; its synthesis has been targeted and its stereocontrolled preparation independently achieved by more than a dozen research groups since the first success.<ref>{{cite journal | last1 = Eichberg | first1 = Michael J. | last2 = Dorta | first2 = Rosa L. | last3 = Lamottke | first3 = Kai | last4 = Vollhardt | first4 = K. Peter C. | year = 2000 | title = The Formal Total Synthesis of (±)-Strychnine via a Cobalt-Mediated [2 + 2 + 2]Cycloaddition | journal = [[Org. Lett.]] | volume = 2 | issue = 16| pages = 2479–2481 | doi = 10.1021/ol006131m | pmid = 10956526 }}</ref><ref>{{cite journal | last1 = Eichberg | first1 = Michael J. | last2 = Dorta | first2 = Rosa L. | last3 = Grotjahn | first3 = Douglas B. | last4 = Lamottke | first4 = Kai | last5 = Schmidt | first5 = Martin | last6 = Vollhardt | first6 = K. Peter C. | year = 2001 | title = Approaches to the Synthesis of (±)-Strychnine via the Cobalt-Mediated [2 + 2 + 2] Cycloaddition: Rapid Assembly of a Classic Framework | journal = [[J. Am. Chem. Soc.]] | volume = 123 | issue = 38| pages = 9324–9337 | doi = 10.1021/ja016333t | pmid = 11562215 | bibcode = 2001JAChS.123.9324E }}</ref>