Five New Cycloartane‐Type Triterpenoid Saponins from Nervilia fordii

Abstract

Five new cycloartane glycosides, nervisides D–H (1–5), were isolated from the AcOEt‐ and H2O‐soluble portions of the 90% EtOH extract of the aerial part of the plant Nervilia fordii. The structures of the isolated glycosides were elucidated by extensive spectroscopic analysis including HR‐ESI‐MS and NMR data. The isolated nervisides D–H were evaluated for the cytotoxic activity in vitro against human‐tumor cell lines (CNE, Hep‐2 and HepG2) with the MTT method.

Nervisides I–J: Unconventional Side-Chain-Bearing Cycloartane Glycosides from Nervilia concolor

“…This article describes the isolation and structural elucidation of two new cycloartane glycosides, namely, nervisides I–J ( 1 – 2 ), from this plant source. Consistent with previously reported structures of Nervilia species, these natural products reveal an unconventional side chain bearing an alkyl substituent at C-24, the absolute configuration of which has been difficult to assign, often leading to an undetermined configuration of this stereogenic center in structurally related compounds, including nervisides A–H isolated from Nervilia fordii [7,8], which were not defined as to this carbon. Such C-24 hydroxymethylated cycloartanes were also repeatedly reported to occur within Passiflora species [9,10,11].…”

“…The NOE cross-peaks between H-1, H 2 -19, and H 3 -29 defined their β-orientation, thereby determining the α-position of the 4-COOH group (Figure 3). The canonical stereochemistry of the ABCD rings [20] was supported by the nearly identical 1 H and 13 C NMR data of 1 with cycloartane triterpenes [21], nervisides A–C [7], nervisides D–H [8], and cyclopassifloic acid series [10], as supported by the key NOE correlations outlined in Figure 3. This only left the relative configuration of the side chain pending assignment.…”

“…Defining the absolute configuration of C-24 alkyl sterols and triterpenes is a vexing problem in NMR spectroscopy that has tentatively been overcome through tailored chromatographic procedures [24,25]. These difficulties result in some authors not defining C-24 absolute configuration on such related scaffolds including cyclotricuspidosides A–C [26] and nervisides A–H [7,8], even though derivatization-based NMR spectroscopy affords reliable outcomes as to this specific point [9,10,27]. To assign the absolute configuration at C-24, 13 C NMR chemical shift calculations of simplified bicyclic models only including cycles C and D were performed using electronic structure methods of the lowest-energy conformer of both C-24 epimers.…”