Application of Residual Dipolar Couplings and Selective Quantitative NOE to Establish the Structures of Tetranortriterpenoids from Xylocarpus rumphii

Abstract

Nine triterpenoid derivatives were isolated from the heartwood of Xylocarpus rumphii and were identified as xylorumphiins E (1), C (2), L (3), and M-R (4-9). Compounds 4-9 have a hemiacetal group in the triterpenoid side chain, making them impossible to purify. Purification was achieved after acetylation and subsequent separation of the epimeric mixtures of acetates; however differentiaition of the R and S epimers was not possible using standard NMR techniques. In one case, the relative configuration of a remotely located stereocenter with respect to the stereocenters in the main skeleton was unambiguously determined using residual dipolar couplings. Dipolar couplings were collected from the sample oriented in compressed poly(methyl methacrylate) gels swollen in CDCl. In another case, the relative configuration was determined using 1D selective quantitative NOE experiments. Xylorumphiin K (10), xyloccensin E, taraxer-14-en-3β-ol, (22S)-hydroxytirucalla-7,24-diene-3,23-dione, and 25-hydroxy-(20S,24S)-epoxydammaran-3-one were isolated from the bark of the same plant. Compounds 3-10 are new compounds. Compounds 1-6 and xyloccensin E were tested at one concentration, 1 × 10 M, in the NCI59 cell one-dose screen but did not show significant activity.

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

“…Many variations exist of those families of compounds. AH, 1,2,3,7-tetramethyl-9-methylene-6,7-dihydro-5H-benzo[a]heptalene (Zarev et al, 2017); AI, 1,5,8-trimethyl-6-oxabicyclo[3.2.1]octan-3one ; AJ,4,4,8,2,3,4a,5,6,8,9,10,11,11a,naphthalene ; AK, taxadiene ; AL,1,3,4,6,2,3,3a,4,6,7,8,9,azulene ; AM, kopsine ; AN, 5-[(3S,10S,13S,17S)-3-hydroxy-10, 13-dimethyl-2,3,4,5,6, 7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pyran-2-one (Schwikkard et al, 2017); AO, 1′,5,5′-trimethylspiro[benzofuran-2,6′-cycloheptene]-3-one ; AP: amorphispirone (Muharini et al, 2017); AQ, cephalotane ; AR, xylorumphiin (Waratchareeyakul et al, 2017); AS, 5-ethyl-1,8a-dimethyl-6-(1,2,3,4-tetramethylcyclohexyl)-5,6,7,8-tetrahydro-1H-isochromen-3-one (Campos et al, 2017); AT, 3′,5,6,7-tetramethyl-5′-propyl-spiro[isobenzo furan-3,2′-tetrahydrofuran]-1-one ; AU, aromaticane ; AV, clerodane (Bisio et al, 2017); AW, 1,7′,9′a-trimethyl spiro[3a,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4, 3′-4,6,7,8,9,9b-hexahydro-3aH-benzo[g] isobenzofuran]-1′,3-dione ; AX, catechin-bound ceanothane-type triterpenoid (Kang et al, 2017a). systematic access to compounds from plant parts: it deals with the use of scalable cultures of plant cells remaining capable of producing these specific chemicals.…”

Deuterium Residual Quadrupolar Couplings: Crossing the Current Frontiers in the Relative Configuration Analysis of Natural Products

“…20 Most of the existing examples, some of them involving difficult structural problems, are based on the use of one-bond proton-carbon residual dipolar couplings (( 13 C-1 H)-RDC), noted also as 1 D CH . 21,22 These key heteronuclear dipolar data can be also soundly combined with: (i) long-range 2,3 D CH constant analysis, [23][24][25] (ii) NOE constraints, 22,25 (iii) J HH data, 21,22,26,27 or (iv) even powder Xray diffraction analysis. 9 Moreover, information on relative orientation of non-protonated carbons can be obtained through the use of the 13 C residual chemical shift anisotropy ( 13 C-RCSA).…”

“…The advent of NMR in weakly aligning media (chiral or not) made it possible to overcome these hurdles by recovering a small fraction of the orientational (tensorial) information inherent to NMR observables and therefore establishing angular restrictions on the relative orientation of the associated tensors . Most of the existing examples, some of them involving difficult structural problems, are based on the use of one-bond proton–carbon residual dipolar couplings (( 13 C– 1 H)-RDCs), also noted as 1 D CH . , These key heteronuclear dipolar data can also be soundly combined with (i) long-range 2,3 D CH constant analysis, − (ii) NOE constraints, , (iii) 3 J HH data, ,,, and (iv) even powder X-ray diffraction analysis . Moreover, information on the relative orientation of nonprotonated carbons can be obtained through the use of the 13 C residual chemical shift anisotropy ( 13 C-RCSA). − Although 13 C-RCSAs are much more technically demanding to measure with enough accuracy compared with RDCs (in particular, when very weakly oriented media are used), the associated experimental protocol is somewhat simplified, as only 13 C–{ 1 H} 1D NMR spectra need to be measured …”

Chemistry and Biology of Novel Meliaceae Limonoids

“…Compounds (357,554) showed moderate insecticidal activity against Plutella xylostella (Diamond back moth) on an artificial diet (Brassica oleracea var. capitata) (200 ppm) with LC 50 value in the concentration of 200 μg/mL was 53.3 and 23.3 % respectively while compounds (177,356,358,359,360,361,552) were inactive 151 . Compounds (356,357,359,554) showed moderate antiviral activity against tobacco mosaic virus (TMV) with inhibitory value in the concentration of 500 μg/mL were 25.4, 29.3, 37.2 and 50 % respectively 151 .…”