Nmr Assignments of Territrems A, B, and C and the Structure of MB₂, the Major Metabolite of Territrem B by Rat Liver Microsomal Fraction

Abstract

The 1H- and 13C-nmr assignments of territrems A, B, and C [1-3] were made by using nOe and 2D nmr techniques. Following the same methods, the structure of MB2 [4], the major product of territrem B incubated with rat liver microsomal fraction, was determined as a hydroxylation product at the pro S methyl group of C-4 of territrem B.

Three New Compounds from Aspergillus terreus PT06-2 Grown in a High Salt Medium

“…The crude extract (31.2 g) was separated by extensive chromatography using silica gel, Sephadex LH-20 and HPLC to give compounds 1 – 15 (Figure 1), including three new compounds: terremides A and B ( 1 , 2 ), terrelactone ( 3 ), and twelve known ones: methyl 3,4,5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate ( 4 ) [15], (+)-butyrolactones I–III ( 5 – 7 ) [16–19], 3-hydroxy-5-[[4-hydroxy-3-(3-methyl-2-buten-1-yl)phenyl]methyl]-4-(4-hydroxyphenyl)-2(5 H )-furanone ( 8 ) [20], aspernolide A ( 9 ) [16], 5-[(3,4-dihydro-2,2-dimethyl-2 H -1-benzopyran-6-yl)-methyl]-3-hydroxy-4-(4-hydroxyphenyl)-2(5 H )-furanone ( 10 ) [18], territrem B ( 11 ) [22], (−)-(1 R ,4 R )-1,4-(2,3)-indomethane-1-methyl-2,4-dihydro-1 H -pyrazino[2,1- b ]quinazoline-3,6-dione ( 12 ) [23], R (−)-6-hydroxymellein ( 13 ) [24], trans -4,6-dihydroxymellein ( 14 ) [25], and (+)-terrein ( 15 ) [26]. …”

Territrem B, a Tremorgenic Mycotoxin That Inhibits Acetylcholinesterase with a Noncovalent yet Irreversible Binding Mechanism

“…MB 2 is a major metabolyte of TRB isolated from rat liver microsomal fraction (17). B, two views of the TRB molecule.…”

Metabolism of Territrem a by Liver Microsomes of Wistar Rats: Identification of the Metabolites and Their Metabolic Sequence

“…Additional evidence for identification of the structure of MA 2 was also obtained by proton and carbon NMR spectral analysis (Tables 2 and 3). The 1 H-NMR singlet signals at H-2 in MA 2 replaced the doublet signals at H-2 in TRA (Ling et al, 1992) MA 2 showed the presence of only three methyl signals, that is, one methyl signal less than TRA, and one methylene group less than MA 1 . The 13 C-NMR spectrum of MA 2 also showed the lack of one methylene group and one methyl signal that were present in MA 1 and TRA.…”

“…Additional evidence of the identification of MA 1 was obtained by proton NMR spectral analysis ( Table 2). The 1 H-NMR spectrum of TRA shows four methyl signals: 4a -CH 3 , 4b -CH 3 , 6a -CH 3 , and 12b -CH 3 (Lee et al, 1992). However, in MA 1 one methyl signal at 4b -CH 3 disappeared and two additional methylene signals appeared at 4b -CH 2 .…”

“…Territrems have a common chemical structure of aromatic, pyran, and terpenoid moiety, but no nitrogen (Lee et al, 1992;Ling et al, 1979Ling et al, , 1984Ling et al, , 1985Ling, 1994). Studies of proton and carbon nuclear magnetic resonance data revealed that the differences in their structures are in their aromatic moiety, namely, 3,4,5-trimethoxyphenyl in TRB, 3-methoxy-4,5-methylenedioxyphenyl in TRA, and 4-hydroxy-3,5-methoxyphenyl in TRC (Lee et al, 1992;Ling et al, 1979Ling et al, , 1984Ling, 1994). In previous studies, it was reported that biotransformation of TRB in liver microsomes of male Wistar rats to four metabolites, designated as MB 1 , MB 2 , MB 3 , and MB 4 , was via oxidation on pyran moiety and O-demethylation on aromatic moiety.…”