RESUMO
Sherman et al. commented on the precedence of enantiodivergence, listing a number of congeneric natural products with opposite chirality. However, these "congeners" are not derived from enantiodivergent biosyntheses. Instead, they are antipodes arising from separate enantiomeric biosyntheses. A distinct feature of the biosynthesis of the cyclic pyrrole-imidazole dimers is the production of antipodal congeners without the corresponding enantiomers.
Assuntos
Reação de Cicloadição , Poríferos/metabolismo , Pirróis/síntese química , AnimaisRESUMO
Cycloaddition is an essential tool in chemical synthesis. Instead of using light or heat as a driving force, marine sponges promote cycloaddition with a more versatile but poorly understood mechanism in producing pyrrole-imidazole alkaloids sceptrin, massadine, and ageliferin. Through de novo synthesis of sceptrin and massadine, we show that sponges may use single-electron oxidation as a central mechanism to promote three different types of cycloaddition. Additionally, we provide surprising evidence that, in contrast to previous reports, sceptrin, massadine, and ageliferin have mismatched chirality. Therefore, massadine cannot be an oxidative rearrangement product of sceptrin or ageliferin, as is commonly believed. Taken together, our results demonstrate unconventional chemical approaches to achieving cycloaddition reactions in synthesis and uncover enantiodivergence as a new biosynthetic paradigm for natural products.
Assuntos
Reação de Cicloadição , Poríferos/metabolismo , Pirróis/síntese química , Animais , Vias Biossintéticas , Estrutura Molecular , Pirróis/química , Pirróis/metabolismo , EstereoisomerismoRESUMO
The pyrrole-imidazole alkaloids have fascinated chemists for decades because of their unique structures. The high nitrogen and halogen contents and the densely functionalized skeletons make their laboratory synthesis challenging. We describe herein an oxidative method for accessing the core skeletons of two classes of pyrrole-imidazole dimers. This synthetic strategy was inspired by the putative biosynthesis pathways and its development was facilitated by computational studies. Using this method, we have successfully prepared ageliferin, bromoageliferin, and dibromoageliferin in their natural enantiomeric form.
Assuntos
Alcaloides/síntese química , Materiais Biomiméticos/química , Imidazóis/síntese química , Pirróis/síntese química , Alcaloides/química , Ciclização , Dimerização , Imidazóis/química , Estrutura Molecular , Pirróis/química , Teoria QuânticaRESUMO
We describe herein an asymmetric synthesis of ageliferin. A Mn(III)-mediated oxidative radical cyclization reaction was used as the key step to construct the core skeleton of this pyrrole-imidazole dimer. This approach resembles the biogenic [4 + 2] dimerization in an intramolecular fashion.
Assuntos
Imidazóis/síntese química , Pirróis/síntese química , Catálise , Imidazóis/química , Manganês/química , Oxirredução , Pirróis/químicaAssuntos
Manganês/química , Pirróis/química , Ciclização , Dimerização , Radicais Livres/química , Estrutura Molecular , OxirreduçãoRESUMO
[reaction: see text] Under the Lewis acid catalysis offered by TiCl(3), SnCl(2) can efficiently mediate the aqueous Barbier reactions between aldehydes and allyl chloride or bromide.