{"id":296,"date":"2016-02-21T09:11:59","date_gmt":"2016-02-21T14:11:59","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=296"},"modified":"2016-02-21T09:11:59","modified_gmt":"2016-02-21T14:11:59","slug":"total-synthesis-of-avermectin-b1a-revisited","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/total-synthesis-of-avermectin-b1a-revisited\/","title":{"rendered":"Total synthesis of avermectin B1a revisited"},"content":{"rendered":"<p>Total synthesis of avermectin B<sub>1a<\/sub> revisited was achieved by Masahiro\u00a0Hirama and co-workers in Tohoku University in Japan.<\/p>\n<p>Avermectins were isolated as compounds possessing anthelmintic activity from the culture broth\u00a0<em>of Streptomycesavermitilis<\/em>\u00a0by\u00a0\u014cmura and co-workers. Owing to their potent anthelmintic and insecticidal activities, as well as their unique pentacyclic architecture, the avermectin family attracted keen interest from synthetic organic chemists. We have recently completed a more efficient and straightforward total synthesis of avermectin B<sub>1a<\/sub>, as compared with previous syntheses.<\/p>\n<p>In the 1970s, \u014cmura\u2019s group at the Kitasato Institute and researchers of Merck Sharp and Dohme Research Laboratories discovered potent antiparasitic agents, the avermectins, from the culture broth of Streptomyces avermitilis (S. avermectinius). Among this family, avermectin B<sub>1a<\/sub> (Figure 1) is the most potent anthelmintic congener. Ivermectin, a mixture of 22,23-dihydro-avermectins B<sub>1a<\/sub> and B<sub>1b<\/sub>, has been used as an important anthelmintic in veterinary fields and for the control of onchocerciasis and lymphatic filariasis in more than 200 million people worldwide.<\/p>\n<p>Masahiro\u00a0Hirama and coworkers achieved an efficient and straightforward total synthesis of avermectin B<sub>1a<\/sub>\u00a0. The highlights of total synthesis include: (i) a vinylogous Mukaiyama aldol reaction to install the C1\u2013C4 carbons; (ii) an intramolecular aldol reaction to form the octahydrobenzofuran; (iii) a formation of trityl oxetane acetal to protect a labile \u03b2-hydroxy aldehyde; (iv) a regioselective installation of C3\u2013C4 double bond; (v) a highly diastereoselective construction of the north segment via coupling of the C22\u2013C28 alkyne and the C15\u2013C21 lactone; (vi) an\u00a0<em>E<\/em>-selective Wittig reaction using trimethylphosphonium salt to connect the polyfunctionalized north and south segments; (vii) an efficient Shiina macrolactonization using a genuine seco acid; (viii) a modified synthesis of the disaccharide and improved glycosylation to afford avermectin B<sub>1a<\/sub>\u00a0. In particular, we should emphasize that a unique and powerful \u2018trityl oxetane acetal\u2019 protecting group strategy worked well to prevent serious epimerization and double bond migration of the sensitive \u03b2-hydroxy carbonyl tetrahydrobenzofuran moiety of\u00a0<strong>1<\/strong>.<\/p>\n<p>&nbsp;<\/p>\n<p>Figure 1<\/p>\n<p><em>Journal of Antibiotics<\/em>\u00a02016,\u00a0(69),\u00a031-50.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Total synthesis of avermectin B1a revisited was achieved by Masahiro\u00a0Hirama and co-workers in Tohoku University in Japan. Avermectins were isolated as compounds possessing anthelmintic activity from the culture broth\u00a0of Streptomycesavermitilis\u00a0by\u00a0\u014cmura [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/296"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=296"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/296\/revisions"}],"predecessor-version":[{"id":297,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/296\/revisions\/297"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=296"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=296"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=296"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}