Publication Date:
2011-11-05
Description:
Many natural products contain a C = C double bond through which various other derivatives can be prepared; the stereochemical identity of the alkene can be critical to the biological activities of such molecules. Catalytic ring-closing metathesis (RCM) is a widely used method for the synthesis of large unsaturated rings; however, cyclizations often proceed without control of alkene stereochemistry. This shortcoming is particularly costly when the cyclization reaction is performed after a long sequence of other chemical transformations. Here we outline a reliable, practical and general approach for the efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% of the Z isomer owing to control induced by a tungsten-based alkylidene. Utility is demonstrated through the stereoselective preparation of epothilone C (refs 3-5) and nakadomarin A (ref. 6), the previously reported syntheses of which have been marred by late-stage, non-selective RCM. The tungsten alkylidene can be manipulated in air, delivering the products in useful yields with high stereoselectivity. As a result of efficient RCM and re-incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways, even under relatively high substrate concentration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211109/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Miao -- Wang, Chenbo -- Kyle, Andrew F -- Jakubec, Pavol -- Dixon, Darren J -- Schrock, Richard R -- Hoveyda, Amir H -- GM-59426/GM/NIGMS NIH HHS/ -- R01 GM059426/GM/NIGMS NIH HHS/ -- R01 GM059426-12/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Nov 2;479(7371):88-93. doi: 10.1038/nature10563.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22051677" target="_blank"〉PubMed〈/a〉
Keywords:
Alkanes/chemistry
;
Alkenes/chemistry
;
Biological Products/*chemical synthesis/chemistry
;
Carbolines/chemical synthesis/chemistry
;
Catalysis
;
Chemistry Techniques, Synthetic/*methods
;
Cyclization
;
Epothilones/chemical synthesis/chemistry
;
Stereoisomerism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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