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Made available in DSpace on 2021-06-25T11:23:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-23 National Institutes of Health Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) College of Agriculture & Life Sciences of the University of Arizona Center for Scientific Computing (NCC/GridUNESP) of Sa eo Paulo State University (UNESP) Incorporation of the epigenetic modifier suberoylanilide hydroxamic acid (SAHA) into a potato dextrose broth culture of the endophytic fungus Aspergillus sp. AST0006 affected its polyketide biosynthetic pathway providing two new 3-(4-oxopyrano)-chromen-2-ones, aspyranochromenones A (1) and B (2), and the isocoumarin, (-)-6,7-dihydroxymellein (3). Eight additional metabolites (4-11) and two biotransformation products of SAHA (12-13) were also encountered. The planar structures and relative configurations of the new metabolites 1-2 were elucidated with the help of high-resolution mass, 1D and 2D NMR spectroscopic data and the absolute configurations of 1-3 were determined by comparison of experimental and calculated ECD data. Possible biosynthetic pathways to 1 and 2 are presented. (C) 2020 Elsevier Ltd. All rights reserved. Univ Arizona, Coll Agr & Life Sci, Southwest Ctr Nat Prod Res, Sch Nat Resources & Environm, 250 E Valencia Rd, Tucson, AZ 85706 USA Sao Paulo State Univ, Inst Chem, BR-14800900 Araraquara, SP, Brazil Jiangsu Normal Univ, Key Lab Biotechnol Med Plants Jiangsu Prov, 101 Shanghai Rd, Xuzhou 221116, Jiangsu, Peoples R China Univ Arizona, Coll Agr & Life Sci, Sch Plant Sci, Tucson, AZ 85721 USA Fluminense Fed Univ, Chem Inst, Dept Organ Chem, BR-24020141 Niteroi, RJ, Brazil Univ Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, Inst Chem, BR-14800900 Araraquara, SP, Brazil National Institutes of Health: R01 CA90265 National Institutes of Health: P41 GM094060 FAPESP: 2018/05905-5 FAPESP: 2014/25222-9

A reinvestigation of the monoterpene chromane ester enriched fraction from Peperomia obtusifolia usingchiral chromatography led to the identification of a minor peak, which was elucidated by NMR and HRMSas fenchyl-3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3 00 -methyl-2 00 -butenyl)-2-(4 0 -methyl-1 0 ,3 0 -pentadie-nyl)-2H-1-benzopyran-6-carboxylate, the same structure assigned to two other fenchyl esters describedpreviously, pointing out a stereoisomeric relationship among them. Further NMR analysis revealed that itwas actually a mixture of two compounds, whose absolute configurations were determined by VCD mea-surements. Although, almost no vibrational transitions could be assigned to the chiral chromane, theexperimental VCD spectrum was largely opposite to that obtained for the average experimental VCD[(2S,1 000 R,2 000 R,4 000 S +2R,1 000 R,2 000 R,4 000 S)/2] for fenchol derivatives. These results allowed us to assign theputa-tive compounds as a racemic mixture of the chiral chromane esterified with the monoterpene (1S,2S,4R)-fenchol, which had not been identified in our early work. 2012 Elsevier Ltd. All rights reserved.

Previous analysis of the ECD spectra of two prenylated benzopyrans isolated from Peperomia obtusifolia, by means of the helicity rule for the chromane chromophore, resulted in the incorrect assignment of their absolute configuration, (S) instead of (R) for a deduced P-helicity of the chromane ring for the (+)-enantiomers. This was discovered by the application of DFT calculations and VCD spectroscopy. Experimental and calculated (B3LYP/6-31G(d)) VCD and IR spectra were compared, and a definitive absolute configuration of (+)-1 and (+)-2 is reassigned directly in solution as (R). The assumption of equatorial positioning of bulky groups, shown here to be invalid for the title molecules, is the underlying cause of the previous incorrect assignment of absolute configuration. Moreover, TDDFT (B3LYP/6-311++G(2d,2p)//B3LYP/6-31G(d)) calculations of ECD spectra have shown that both P- and M-helicity of the heterocyclic ring, for a given absolute configuration, lead to the same sign for the 1Lb ECD band, thus bringing into question the validity of the empirical ECD helicity rule for chromane molecules.