Synthesis and biology of 1,4-benzodioxane lignan natural products

Several biologically active compounds structurally include the enantiopure 2-substituted-1,4-benzodioxane scaffold. The straightforward racemization that affects reactions involving most of the common chemical reactives is thus a crucial issue. The developing of a completely stereo-controlled synthetic route that does not affect the enantiomeric excess is consequently mandatory. It is also important to set up a reliable chiral HPLC method, able to follow the reaction, and to improve the synthetic performances. Here, we report the chiral investigation of two different synthons, we specifically evaluated the synthetic pathways that could be run in order to afford them, avoiding the racemization processes, which could normally occur in basic conditions. In addition, we developed peculiar chiral HPLC methods in order to resolve the enantiomers, define the enantiomeric excess, and fully characterize these compounds.

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“…A similar behavior was already seen for WB4101 analogues and other 1,4‐benzodioxane lignan natural products …”

Section: Introductionsupporting

confidence: 81%

How do reaction conditions affect the enantiopure synthesis of 2‐substituted‐1,4‐benzodioxane derivatives?

et al. 2018

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“…tomato DC3000 (Zamioudis et al, 2014). The enhanced disease resistance of A. thaliana against different pathogens can be associated with the structure of the coumarin-type compounds produced, since different substituents in the backbone of coumarins and lignans can influence biological activity (Weinmann, 1997; Apers et al, 2003; Borges et al, 2005; Zhang et al, 2014; Pilkington and Barker, 2015). …”

Section: Discussionmentioning

confidence: 99%

“…Regarding plant coumarinolignans, the current knowledge on their biological activities is mostly pharmacological, derived from the ethno-medical utilization of some plant species (Begum et al, 2010; Zhang et al, 2014; Pilkington and Barker, 2015). Known activities of cleomiscosins include liver protection, cytotoxicity against lymphocytic leukemia cells, immunomodulation, and others.…”

Section: Discussionmentioning

confidence: 99%

Accumulation and Secretion of Coumarinolignans and other Coumarins in Arabidopsis thaliana Roots in Response to Iron Deficiency at High pH

et al. 2016

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Root secretion of coumarin-phenolic type compounds has been recently shown to be related to Arabidopsis thaliana tolerance to Fe deficiency at high pH. Previous studies revealed the identity of a few simple coumarins occurring in roots and exudates of Fe-deficient A. thaliana plants, and left open the possible existence of other unknown phenolics. We used HPLC-UV/VIS/ESI-MS(TOF), HPLC/ESI-MS(ion trap) and HPLC/ESI-MS(Q-TOF) to characterize (identify and quantify) phenolic-type compounds accumulated in roots or secreted into the nutrient solution of A. thaliana plants in response to Fe deficiency. Plants grown with or without Fe and using nutrient solutions buffered at pH 5.5 or 7.5 enabled to identify an array of phenolics. These include several coumarinolignans not previously reported in A. thaliana (cleomiscosins A, B, C, and D and the 5′-hydroxycleomiscosins A and/or B), as well as some coumarin precursors (ferulic acid and coniferyl and sinapyl aldehydes), and previously reported cathecol (fraxetin) and non-cathecol coumarins (scopoletin, isofraxidin and fraxinol), some of them in hexoside forms not previously characterized. The production and secretion of phenolics were more intense when the plant accessibility to Fe was diminished and the plant Fe status deteriorated, as it occurs when plants are grown in the absence of Fe at pH 7.5. Aglycones and hexosides of the four coumarins were abundant in roots, whereas only the aglycone forms could be quantified in the nutrient solution. A comprehensive quantification of coumarins, first carried out in this study, revealed that the catechol coumarin fraxetin was predominant in exudates (but not in roots) of Fe-deficient A. thaliana plants grown at pH 7.5. Also, fraxetin was able to mobilize efficiently Fe from a Fe(III)-oxide at pH 5.5 and pH 7.5. On the other hand, non-catechol coumarins were much less efficient in mobilizing Fe and were present in much lower concentrations, making unlikely that they could play a role in Fe mobilization. The structural features of the array of coumarin type-compounds produced suggest some can mobilize Fe from the soil and others can be more efficient as allelochemicals.

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“…[1] Fore xample,1 ,4-benzodioxane lignans represented by silybin A [2] are ag roup of natural products that exhibit aw ide range of interesting biological activities,s uch as hepatoprotective, anticancer,and antioxidant activity.Doxazosin [3] is aselective a1-adrenoceptor antagonist with a1 ,4-benzodioxane moiety that is used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia. [1] Fore xample,1 ,4-benzodioxane lignans represented by silybin A [2] are ag roup of natural products that exhibit aw ide range of interesting biological activities,s uch as hepatoprotective, anticancer,and antioxidant activity.Doxazosin [3] is aselective a1-adrenoceptor antagonist with a1 ,4-benzodioxane moiety that is used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia.…”

mentioning

confidence: 99%

“…Over past several years,our research group has focused on the development of efficient chiral monophosphorus ligands for asymmetric catalysis.T he success of those conformationally well defined and sterically bulky P-stereogenic monophosphorus ligands based on ad ihydrobenzo[d]- [1,3]oxaphosphole framework in various asymmetric carbon-carbon bond-forming reactions [16] prompted us to investigate the alkene aryloxyarylation between 2-((2-methylallyl)oxy)phenol (1a)a nd bromobenzene (2a). Ther eactions were performed in toluene at 110 8 8Cunder nitrogen for 18 hw ith NaOtBu as the base in the presence of [Pd 2 (dba) 3 ] (2 mol %) and achiral ligand (4 mol %; Table 1, entries [1][2][3][4][5][6][7][8].…”

mentioning

confidence: 99%

Synthesis of Chiral 1,4‐Benzodioxanes and Chromans by Enantioselective Palladium‐Catalyzed Alkene Aryloxyarylation Reactions

Wang

et al. 2016

Angew Chem Int Ed

105

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A highly enantioselective alkene aryloxyarylation led to the high-yielding formation of a series of 1,4-benzodioxanes, 1,4-benzooxazines, and chromans containing quaternary stereocenters with excellent enantioselectivity. The sterically bulky and conformationally well defined chiral monophosphorus ligand L4 or L5 was responsible for the high reactivity and enantioselectivity of these transformations. The application of this method to the synthesis of the chiral chroman backbone of α-tocopherol was demonstrated.

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Synthesis and biology of 1,4-benzodioxane lignan natural products

Cited by 46 publications

References 96 publications

How do reaction conditions affect the enantiopure synthesis of 2‐substituted‐1,4‐benzodioxane derivatives?

How do reaction conditions affect the enantiopure synthesis of 2‐substituted‐1,4‐benzodioxane derivatives?

Accumulation and Secretion of Coumarinolignans and other Coumarins in Arabidopsis thaliana Roots in Response to Iron Deficiency at High pH

Synthesis of Chiral 1,4‐Benzodioxanes and Chromans by Enantioselective Palladium‐Catalyzed Alkene Aryloxyarylation Reactions

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