Total synthesis of cytotoxic metabolite ( ± )-desmethyldiaportinol from Ampelomyces sp.

Abstract

A concise total synthesis of ( ± )-desmethyldiaportinol isolated from Ampelomyces sp. is described. Microwave-assisted cyclocondensation of 3,5-dimethoxyhomopthalic acid with 3,4-dibromobutanoyl chloride afforded the 3-(2,3-dibromopropyl)-6, 8-dimethoxyisocoumarin in 2-3 min as the pivotal step. The 3,4-dibromobutanoyl chloride was itself synthesised from 3-butenoic acid via bromination in carbon tetrachloride at room temperature to yield 3,4-dibromobutanoic acid followed by reaction with thionyl chloride. The replacement of bromo- by hydroxyl substituent was achieved under mild conditions involving the refluxing in a mixture of acetone and water to provide ( ± )-3-(2,3-dihydroxypropyl)-6,8-dimethoxyisocoumarin which on complete demethylation furnished the title natural product.

Naturally Occurring Isocoumarins Derivatives from Endophytic Fungi: Sources, Isolation, Structural Characterization, Biosynthesis, and Biological Activities

“…Besides, the total synthesis provides important information and an additional confirmation for characterization of these metabolites structures. Furthermore, it allows the synthesis of analogs with improved biological efficiencies [11,34,35]. The X-ray structure crystallographic analysis of the crystalline derivatives is another tool for the absolute configuration determination.…”

“…Isocoumarins (1H-2-benzopyran-1-ones or isochromene derivatives) are a class of biosynthetically, structurally, and pharmacologically intriguing natural products, which chemistry field due to their sustainability to biosynthesize structurally diverse and bioactive molecules, some of which are important agrochemicals and pharmaceuticals [9,10]. Isocoumarins (1H-2-benzopyran-1-ones or isochromene derivatives) are a class of biosynthetically, structurally, and pharmacologically intriguing natural products, which are coumarins isomers with a reversed lactone moiety that could possess 6,8-dioxygenated pattern, 3-(un)substituted phenyl ring or 3-alkyl chain (C1-C17) [11,12]. The oxygenation could exist at one or more of the six free positions of the isocoumarin skeleton.…”

“…Thus, isocoumarin framework has been explored in various areas, including drug discovery, pharmaceutical and medicinal chemistry, and organic synthesis [13]. It has been reported that these metabolites possess various bioactivities: antimicrobial, cytotoxic, algicidal, antiallergic, immunomodulatory, antimalarial, plant growth regulatory, and acetylcholinesterase and protease inhibitors [11,[17][18][19][20]. This review aims to give a highlight on the naturally occurring isocoumarins derivatives reported from endophytic fungi, focusing on the period from 2000 to July 2019.…”

Secondary Metabolites from the Endophytic Fungus Xylaria sp. hg1009

“…Unfortunately, studies about the absolute configuration of 7 was restricted due to the sample shortage (1.1 mg), therefore, the configuration of C-11 couldn’t be determined under the current situation. Consequently, 7 was named 3-(2,3-dihydroxypropyl)-6,8-dimethoxyisocoumarin, and defined as a new natural product, previously reported as a reactant for the total synthesis of desmethyldiaportinol [ 23 ].…”

A Chiral Pool Approach for Total Synthesis of (+)‐Diaportinol, (−)‐Peniisocoumarin H and (+) & (−)‐Desmethyldiaportinol; Their Structural Revision

“…Till to date there is no synthesis was reported for diaportinol, on the other hand a racemic approach for the desmethyldiaportinol was reported by Saeed et.al. [9] The continuous ambiguity over the absolute stereochemistry of diaportinol and its analogs since last two decades motivated us to synthesize these small aromatic polyketides. We adopted a convergent approach that uses both L-& D-malic acids to introduce the stereogenic center in both the enantiomers.…”