Cycloclavine

{{Chembox

| ImageFile = Cycloclavine.svg

| ImageSize = 150px

| ImageAlt =

| IUPACName = 6,8-Dimethyl-8,10-cycloergoline

| SystematicName = (1aS,3aR,9bS)-1a,3-Dimethyl-1a,2,3,3a,4,6-hexahydro-1H-cyclopropa[c]indolo[4,3-ef]indole

| OtherNames =

|Section1={{Chembox Identifiers

| CASNo = 26057-57-8

| CASNo_Ref = {{cite web |title=KNApSAcK Metabolite Information - C00011221 |url=http://www.knapsackfamily.com/knapsack_core/information.php?word=C00011221 |website=www.knapsackfamily.com}}{{Cascite|changed|}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = XRQ6TJ7KL8

| PubChem = 101316916

| ChemSpiderID = 25991549

| StdInChI=1S/C16H18N2/c1-15-8-16(15)11-4-3-5-12-14(11)10(7-17-12)6-13(16)18(2)9-15/h3-5,7,13,17H,6,8-9H2,1-2H3/t13-,15-,16-/m0/s1

| StdInChIKey = ZWJHDICNUKHUGE-BPUTZDHNSA-N

| SMILES = [H][C@@]12CC3=CNC4=C3C(=CC=C4)[C@]11C[C@]1(C)CN2C}}

|Section2={{Chembox Properties

| C=16 | H=18 | N=2

| Appearance =

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|Section3={{Chembox Hazards

| MainHazards =

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Cycloclavine is an ergot alkaloid. It was first isolated in 1969 from seeds of Ipomoea hildebrandtii vatke.{{cite journal | doi = 10.1016/S0040-4020(01)83095-7| pmid = 5373534| title = Cycloclavin, ein neues alkaloid aus Ipomoea hildebrandtii vatke—71| journal = Tetrahedron| volume = 25| issue = 24| pages = 5879–87| year = 1969| last1 = Stauffacher| first1 = D| last2 = Niklaus| first2 = P| last3 = Tscherter| first3 = H| last4 = Weber| first4 = H.P| last5 = Hofmann| first5 = A}} The first total synthesis of (±)-cycloclavine was published in 2008 by Szántay.{{cite journal | last1 = Incze | first1 = M. | last2 = Dörnyei | first2 = G. | last3 = Moldvai | first3 = I. | last4 = Temesvári-Major | first4 = E. | last5 = Egyed | first5 = O. | last6 = Szántay | first6 = C. | year = 2008 | title = New routes to clavine-type ergot alkaloids. Part 2: Synthesis of the last, so far not yet synthesized member of the clavine alkaloid family, (±)-cycloclavine| journal = Tetrahedron | volume = 64 | issue = 13| pages = 2924–2929 | doi=10.1016/j.tet.2008.01.101}} Further reports came from Wipf and Petronijevic,{{cite journal | last1 = Petronijevic | first1 = F. R. | last2 = Wipf | first2 = P | year = 2011 | title = Total Synthesis of (±)-Cycloclavine and (±)-5-epi-Cycloclavine| journal = J. Am. Chem. Soc. | volume = 133 | issue = 20| pages = 7704–7707 | doi=10.1021/ja2026882| pmc = 3111057 | pmid=21517102}} Cao{{cite journal | last1 = Wang | first1 = W. | last2 = Lu | first2 = J.-T. | last3 = Zhang | first3 = H.-L. | last4 = Shi | first4 = Z.-F. | last5 = Wen | first5 = J. | last6 = Cao | first6 = X.-P | year = 2013 | title = Formal Synthesis of (±)-Cycloclavine| journal = J. Org. Chem. | volume = 79 | issue = 1 | pages = 122–127 | doi=10.1021/jo4023588 | pmid = 24279324}} and Brewer.{{cite journal | last1 = Jabre | first1 = N. D. | last2 = Watanabe | first2 = T. | last3 = Brewer | first3 = M. | year = 2014 | title = Formal and total synthesis of (±)-cycloclavine| journal = Tetrahedron Lett. | volume = 55 | issue = 1 | pages = 197–199 | doi=10.1016/j.tetlet.2013.10.152| pmc = 3915717 | pmid=24511164}} In 2016, Wipf and McCabe completed an 8-step asymmetric synthesis of (–)-cycloclavine,{{cite journal|doi=10.1002/ange.201608820 | volume=129 | title=Eight-Step Enantioselective Total Synthesis of (−)-Cycloclavine | journal=Angewandte Chemie | pages=330–333 | last1 = McCabe | first1 = Stephanie R.| year=2017 | issue=1 | pmc=5195887 | pmid=27860203}} and in 2018, they expanded this approach toward (+)-cycloclavine and a biological characterization of the binding profile of both enantiomers on 16 brain receptors.{{Cite journal|last1=Wipf|first1=Peter|last2=McCabe|first2=Stephanie|date=2018-11-20|title=Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine|journal=Synthesis|language=en|doi=10.1055/s-0037-1610395|issn=0039-7881|volume=51|pages=213–224|doi-access=free}} Natural (+)- and unnatural (–)-cycloclavine demonstrated significant stereospecificity and unique binding profiles in comparison to LSD (lysergic acid diethylamide), psilocin, and DMT. Differential 5-HT receptor affinities, as well as novel sigma-1 receptor properties, suggest potential future therapeutic opportunities of clavine alkaloid scaffolds.