Publication Date:
2015-09-17
Description:
Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine. Although efficient laboratory synthesis of alkaloids would enable the study and optimization of their biological properties, their preparation is often complicated by the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways--for example, through stereochemical instability and neighbouring group participation. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen; however, the use of protecting groups typically introduces additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies. Here we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest linear sequence) from simple pyrrole-based starting materials. The route uses several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages of beginning with aromatic reagents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583359/" 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/PMC4583359/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parr, Brendan T -- Economou, Christos -- Herzon, Seth B -- F32 GM110898/GM/NIGMS NIH HHS/ -- GM110898-01A1/GM/NIGMS NIH HHS/ -- T32GM067543/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):507-10. doi: 10.1038/nature14902. Epub 2015 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26375010" target="_blank"〉PubMed〈/a〉
Keywords:
Anti-HIV Agents/*chemical synthesis/*chemistry
;
Biological Products/chemical synthesis/chemistry
;
Guanidine/*analogs & derivatives/chemical synthesis/chemistry
;
Nitrogen/chemistry
;
Pyrroles/*chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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