Total synthesis of isocladosporin and 3- epi -isocladosporin

Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

“…Cladosporin has been shown to inhibit the activity of Plasmodium LysRS ( 19 ). Another metabolite isolated from Cladosporium cladosporioides , isocladosporin, exhibits antibacterial, antifungal, and plant-growth-inhibitory activity ( 23 ). Cladosporin and isocladosporin are composed of a tetrahydropyran (THP) ring (2,6-disubstituted tetrahydropyran) and a δ-valerolactone with a fused 1,3-dihydroxybenzene ring ( Fig.…”

“…3-Epi-isocladosporin ( Fig. 7A ) is an isomer of isocladosporin ( 23 ). To test the efficacy of these compounds on L. donovani , WT log-phase promastigotes were cultured with increasing concentrations of these compounds.…”

“…Isocladosporin, isolated from the fungus Cladosporium cladosporioides , is also composed of a THP ring similar to cladosporin. 3-Epi-isocladosporin is an isomer of isocladosporin ( 23 ). Cladosporin mimics the adenosine part of ATP and hence interacts with the catalytic site of the LysRS ( 30 ).…”

“…Heterozygous knockout mutants of Ld LysRS-1 showed reduced growth and were attenuated in their infectivity, indicating the essentiality of this protein. Cladosporin, a fungal secondary metabolite, and 3-epi-isocladosporin, an isoform of isocladosporin ( 22 , 23 ), showed antileishmanial activity in both the promastigote and intracellular amastigote stages in vitro . Both drugs were found to be effective in inhibiting the aminoacylation activity of the recombinant Ld LysRS-1.…”

Six-Membered Ring Systems

“…The total synthesis of natural carbazole[2,1-b]-2H-pyrans koenidine and mahanimbine (16JA13870), koenine, koenimbine, koenigine, and koenigicin (16S150); of chroman-type bryostatins (16JA13415), 3,14-didehydroxyisogarcinol and garcimultiflorone A stereoisomers (16JA14789), paeoveitol (16OL3698), and xiamenmycin A (16OBC1805); of polycyclic bischroman-type kuwanon X and Y and kuwanol A (16OL360); of biscoumarins valoneic and woodfordinic acids (16SL859); of isocoumarin legioliulin (16TL3942); of 3,4-dihydroisocoumarin isocladosporin and 3-epi-isocladosporin (16TL53); of flavone derivatives such as artocapin (16H(93)310), 2 ′ ,3,5 ′ ,6,7,8-hexamethoxyflavone (16SL1725), and houttuynoid B (16CEJ2935); of cytotoxic hexahydro-1H-xanthene (+)-psiguadial B (16JA9803); of pyrano[2,3-b]chromantype teadenols A and B (16OBC10783), mirabiquinone A, and its methyl derivatives (16S761); of xanthene-type compound (−)-siccanin (16SL96); of three C-glycosyl xanthones mangiferin, homomangiferin, and neomangiferin (16OBC8821) and the prenylated xanthone elliptoxanthone A (16SL2229); of cytotoxic polycyclic tetrahydroxanthone kibdelone C and its simplified derivatives (16JA10561); and of HIV-1 integrase inhibitor containing a 1,3-dioxine moiety integrastatin B (16OL1458) have also been surveyed.…”