{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:35:30Z","timestamp":1760852130990},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T00:00:00Z","timestamp":1095724800000},"content-version":"vor","delay-in-days":4647,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chirality"],"published-print":{"date-parts":[[1992,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The synthesis of the eight stereoisomers of muscarine has been efficiently accomplished by utilizing the two enantiomers of lactic esters as starting material. The synthetic strategy is based on a SnCl<jats:sub>4<\/jats:sub>\u2010catalyzed addition of allyltrimethylsilane to O\u2010protected lactic aldehydes followed by an iodocyclization process. All the final derivatives possess an enantiomeric excess higher than 98%. The four pairs of enantiomers bound to M<jats:sub>1<\/jats:sub>, M<jats:sub>2<\/jats:sub>, and M<jats:sub>3<\/jats:sub> muscarinic receptor subtypes in membranes from cerebral cortex, heart, and salivary glands, respectively, and recognized heterogeneous states of the receptors. Of the eight isomers, only natural muscarine (+)\u2010<jats:bold>1<\/jats:bold> recognized three affinity states of the M<jats:sub>2<\/jats:sub> receptor. The compound was also the only one to show selectivity in the binding study, demonstrating 37\u2010 to 44\u2010fold higher affinity for the M<jats:sub>2<\/jats:sub> than for the M<jats:sub>1<\/jats:sub> or M<jats:sub>3<\/jats:sub> receptors. In addition, the compounds were tested in functional assays on isolated guinea pig atria (M<jats:sub>2<\/jats:sub> receptors) and ileum (mixed population of M<jats:sub>2<\/jats:sub> and M<jats:sub>3<\/jats:sub> receptors) and their muscarinic potencies were determined. Among the eight isomers, again only (+)\u2010<jats:bold>1<\/jats:bold> enantiomer was found to be very active on both tissues. Its potency was more than two orders of magnitude higher than that of its enantiomer (\u2212)\u2010<jats:bold>1<\/jats:bold> as well as the other six isomers. The eudismic ratios (E.R.) deduced from the two functional tests were 324 and 331. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/chir.530040406","type":"journal-article","created":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T11:21:25Z","timestamp":1105096885000},"page":"230-239","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and pharmacological investigation of stereoisomeric muscarines"],"prefix":"10.1002","volume":"4","author":[{"given":"Marco De","family":"Amici","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clelia","family":"Dallanoce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo De","family":"Micheli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enzo","family":"Grana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Dondi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert","family":"Ladinsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovannibattista","family":"Schiavi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Zonta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,21]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"127","volume-title":"Stereochemistry and Biological Activity of Drugs","author":"Dahlbom R.","year":"1983"},{"key":"e_1_2_1_3_2","first-page":"315","volume-title":"Chemical Pharmacology of the Synapse","author":"Triggle D.J.","year":"1976"},{"key":"e_1_2_1_4_2","first-page":"465","article-title":"Chemistry and pharmacology of muscarine, muscarone, and some related compounds","volume":"13","author":"Waser P.G.","year":"1961","journal-title":"Pharmacol.Rev."},{"key":"e_1_2_1_5_2","volume-title":"Trends in Pharmacological Science 10 (Suppl. Subtypes of Muscarinic Receptors IV)","author":"Levine R.R.","year":"1989"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.10.030187.001211"},{"key":"e_1_2_1_7_2","first-page":"859","article-title":"Nitrile oxides in medicinal chemistry. 3. Synthesis and bioenantioselectivity of (+)\u2010 and (\u2212)\u20102\u2010methyl\u20105\u2010;[(dimethylamino)\u2010methyl]\u20103\u2010oxo\u2010isoxazolidine methiodide","volume":"45","author":"De Amici M.","year":"1990","journal-title":"Il Farmaco"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00001a015"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","unstructured":"This method was successful in a similar case:Mori K. Tamura H.Synthesis of mono\u2010 and sesquiterpenoids. X. Synthesis of sporogen\u2010AO 1(13\u2010deoxyphomenone) a sporigen sesquiterpene fromAspergillus oryzae.Liebigs Ann.Chem.97\u2013105 1988.","DOI":"10.1002\/jlac.198819880202"},{"key":"e_1_2_1_10_2","first-page":"327","volume-title":"The Alkaloids","author":"Wang P.\u2010C.","year":"1984"},{"key":"e_1_2_1_11_2","doi-asserted-by":"crossref","unstructured":"(a)Amouroux R. Gerin B. Chastrette M.Simple and very stereoselective synthesis of d l\u2010muscarine.Tetrahedron Lett.4341\u20134344 1982.","DOI":"10.1016\/S0040-4039(00)85595-1"},{"key":"e_1_2_1_11_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)96784-5"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00196a022"},{"key":"e_1_2_1_13_2","unstructured":"Throughout the paper we will represent the structure of the sole enantiomers derived from (S)\u2010ethyl lactate even if the reaction sequence was also carried out on (R)\u2010methyl lactate."},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00403a075"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","unstructured":"(a)Mitsunobu O.The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products.Synthesis1\u201328 1981.","DOI":"10.1055\/s-1981-29317"},{"key":"e_1_2_1_15_3","doi-asserted-by":"crossref","unstructured":"(b)Bandzouzi A. Chapleur Y.Dichloromethylenation of sugar \u03b3\u2010lactones: A stereospecific synthesis ofL\u2010(+)\u2010muscarine andL\u2010(+)\u2010epimuscarine toluene\u2010p\u2010sulfonates.J.Chem.Soc.Perkin I661\u2013664 1987.","DOI":"10.1039\/P19870000661"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00869a035"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00174a006"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00225a031"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo01261a013"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(86)90409-1"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(82)90066-2"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(86)90410-8"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90568-1"},{"key":"e_1_2_1_25_2","first-page":"617","article-title":"Characterization of muscarinic receptors in guinea pig ileum longitudinal smooth muscle","volume":"33","author":"Giraldo E.","year":"1988","journal-title":"Mol.Pharmacol."},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90846-7"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb11327.x"}],"container-title":["Chirality"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchir.530040406","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chir.530040406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T17:25:42Z","timestamp":1698081942000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/chir.530040406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,1]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1992,1]]}},"alternative-id":["10.1002\/chir.530040406"],"URL":"https:\/\/doi.org\/10.1002\/chir.530040406","archive":["Portico"],"relation":{},"ISSN":["0899-0042","1520-636X"],"issn-type":[{"value":"0899-0042","type":"print"},{"value":"1520-636X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,1]]}}}