Simonic Acid Research Articles

Four new pentasaccharide resin glycosides from Ipomoea cairica with strong α-glucosidase inhibitory activity.

Six pentasaccharide resin glycosides from Ipomoea cairica, including four new acylated pentasaccharide resin glycosides, namely cairicoside I–IV (1–4) and the two known compounds cairicoside A (5) and cairicoside C (6), were isolated from the aerial parts of Ipomoea cairica. Their structures were established by a combination of spectroscopic, including two dimensional (2D) NMR and chemical methods. The core of the six compounds was simonic acid A, and they were esterfied the same sites, just differing in the substituent groups. The lactonization site of the aglycone was bonded to the second saccharide moiety at C-2 in 1–4, and at C-3 in 5–6. Compounds 1 and 5, 4 and 6 were two pairs of isomers. The absolute configuration of the aglycone in 1–6 which was (11S)-hydroxyhexadecanoic acid (jalapinolic acid) was established by Mosher’s method. Compounds 1–4 have been evaluated for inhibitory activity against α-glucosidase, which all showed inhibitory activities.

Batatins VIII–XI, Glycolipid Ester-Type Dimers from Ipomoea batatas

Sweet potato (Ipomoea batatas) is native to the tropics of Central and South America, where many varieties have been consumed for more that 5000 years. In developing countries, this crop is a recognized effective food for fighting malnutrition. Purification of the minor lipophilic glicolipids found in the n-hexane-soluble resin glycosides from the white-skinned variety was performed by preparative-scale recycling HPLC. Application of column overload, peak shaving, heart cutting, and recycling techniques permitted the purification of four new oligosaccharide ester-type dimer derivatives of jalapinolic acid, batatins VIII-XI (1-4). The structural characterization of these complex lipo-oligosaccharides was performed through NMR spectroscopy and MS, indicating that batatins VIII-XI (1-4) possess an oligomeric structure consisting of two pentasaccharide units of the known simonic acid B.

Cytotoxic resin glycosides from Ipomoea aquatica and their effects on intracellular Ca2+ concentrations.

Eleven new resin glycosides, aquaterins I-XI (1-11), were isolated from the whole plants of Ipomoea aquatica. The structures of 1-11 were elucidated by a combination of spectroscopic and chemical methods. They were found to be partially acylated tetra- or pentasaccharides derived from simonic acid B and operculinic acids A and C. The site of the aglycone macrolactonization was placed at C-2 or C-3 of the second saccharide moiety, while the two acylating residues could be located at C-2 (or C-3) of the second rhamnose unit and at C-4 (or C-3) on the third rhamnose moiety. All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Compound 4 exhibited the most potent activity against HepG2 cells with an IC50 value of 2.4 μM. Cell cycle analysis revealed 4 to inhibit the proliferation of HepG2 cells via G0/G1 arrest and apoptosis induction. In addition, compounds 1-4, 7, 9, and 10 were found to elevate Ca(2+) in HepG2 cells, which might be involved in the regulation of the cytotoxic activities observed.

Resin Glycosides from the Yellow-Skinned Variety of Sweet Potato (Ipomoea batatas)

Native to tropical America, Ipomoea batatas has been cultivated for over 5000 years in Mexico. The yellow-skinned tuber crop variety, with an orange flesh, has a higher nutritional value than potato. Raw sweet potato can cause a purge due to its resin glycoside content. Purification of the chloroform-soluble resin glycosides from the roots of this variety was accomplished by preparative-scale HPLC, which allowed for the collection of six oligosaccharides, batatin VII (1) and batatinosides VII-IX (2-4), all of novel structure, together with the known resin glycosides pescaprein I and batatinoside IV. High-field NMR spectroscopy and FAB mass spectrometry were used to characterize each structure, identifying operculinic acid A for compounds 2 and 4, and simonic acid B for 3, as their pentasaccharide glycosidic cores. Batatin VII (1) represents a dimer of the know batatinoside IV, consisting of two units of simonic acid B.

Pentasaccharide resin glycosides from Ipomoea cairica and their cytotoxic activities

Six partially acylated pentasaccharide resin glycosides, cairicosides A-F, were isolated from the aerial parts of Ipomoea cairica. These compounds were characterized as a group of macrolactones of simonic acid A, partially acylated with different organic acids. The lactonization site of 11S-hydroxyhexadecanoic acid (jalapinolic acid) was bound to the second saccharide moiety at C-3 in cairicosides A-E, while at C-2 in cairicoside F. Structures were established by spectroscopic and chemical methods. Compounds cairicosides A-E exhibited moderate cytotoxicity against a small panel of human tumor cell lines with IC50 values in the range of 4.28-14.31μM.

Modulators of antibiotic activity from Ipomoea murucoides

Reinvestigation of the CHCl3-soluble extract from the flowers of Ipomoea murucoides, through preparative-scale recycling HPLC, yielded three pentasaccharides of 11-hydroxyhexadecanoic acid, murucoidins XVII-XIX, in addition to the known murucoidin III and V, all of which were characterized by NMR spectroscopy and mass spectrometry. These compounds were found to be macrolactones of the known pentasaccharides simonic acid B and operculinic acid A. The acylating groups corresponded to acetic, (2S)-methyl-butyric, (E)-cinnamic and octanoic acids. The esterification sites were established at the C-2 of the second rhamnose and C-3 and C-4 of the third rhamnose. The aglycone lactonization was placed at C-2 or C-3 of the first rhamnose. Bioassays for modulation of antibiotic activity were performed against multidrug-resistant strains of Staphylococcus aureus, Escherichia coli Rosetta-gami, and two nosocomial pathogens: Salmonella enterica sv. Typhi and Shigella flexneri. The tested glycolipids did not act as cytotoxic (IC50>4 μg/mL) nor as antimicrobial (MIC>128 μg/mL) agents. However, they exerted a potentiation effect on clinically useful antibiotics against the tested bacteria by increasing their antibiotic susceptibility up to four-fold at concentrations of 25 μg/mL.

Pentasaccharide Resin Glycosides from Ipomoea pes-caprae

Pescapreins XXI-XXX (1-10), pentasaccharide resin glycosides, together with the known pescapreins I-IV and stoloniferin III were isolated from the aerial parts of Ipomoea pes-caprae (beach morning-glory). The pescapreins are macrolactones of simonic acid B, partially esterified with different fatty acids. The lactonization site of the aglycone, jalapinolic acid, was located at C-2 or C-3 of the second saccharide moiety. Their structures were established by a combination of spectroscopic and chemical methods. Compounds 1-10 were evaluated for their potential to modulate multidrug resistance in the human breast cancer cell line MCF-7/ADR. The combined use of these new compounds at a concentration of 5 μg/mL increased the cytotoxicity of doxorubicin by 1.5-3.7-fold.

Characterization of a xylose containing oligosaccharide, an inhibitor of multidrug resistance in Staphylococcus aureus, from Ipomoea pes-caprae

Pescaprein XVIII ( 1), a type of bacterial efflux pump inhibitor, was obtained from the CHCl 3-soluble resin glycosides of beach morning glory ( Ipomoea pes-caprae). The glycosidation sequence for pescaproside C, the glycosidic acid core of the lipophilic macrolactone 1 containing d-xylose and l-rhamnose, was characterized by means of several NMR techniques and FAB mass spectrometry. Recycling HPLC also yielded eight non-cytotoxic bacterial resistance modifiers, the two pescapreins XIX ( 2) and XX ( 3) as well as the known murucoidin VI ( 4), pecapreins II ( 6) and III ( 7), and stoloniferins III ( 5), IX ( 8) and X ( 9), all of which contain simonic acid B as their oligosaccharide core. Compounds 1– 9 were tested for in vitro antibacterial and resistance-modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. All of the pescapreins potentiated the action of norfloxacin against the NorA over-expressing strain by 4-fold (8 μg/mL from 32 μg/mL) at a concentration of 25 μg/mL.

Batatinosides II−VI, Acylated Lipooligosaccharides from the Resin Glycosides of Sweet Potato

Sweet potato ( Ipomoea batatas) belongs to the Convolvulaceae (morning glory family) and is native to Mexico and Central America. Its edible tuberous roots have been much appreciated since pre-Hispanic times in Mesoamerica and now play an important role as a basic diet staple and a medicinal plant worldwide. The hexane-soluble extract from roots, through preparative-scale recycling HPLC, yielded five new lipophilic oligosaccharides of jalapinolic acid, batatinosides II-VI ( 1- 5), as well as the known pescapreins I ( 6) and VII ( 7) and murucoidin I ( 8), which are part of the purgative resin glycoside mixture. NMR spectroscopy and FAB mass spectrometry were used to characterize their structures. Compounds 1 and 2 are tetraglycosidic lactones of operculinic acid C. The pentasaccharide structures for compounds 3 and 4 were confirmed to be macrolactones of simonic acid B, and that characterized for 5 was derived from operculinic acid A. The lactonization site of the aglycone was placed at C-3 of the second saccharide unit in all compounds except 4, where it was placed at C-2. All compounds contain an esterifying residue that is composed of a long-chain fatty acid, n-decanoic acid (capric) or n-dodecanoic acid (lauric). In compound 3, an additional short-chain fatty acid, (2 S)-methylbutyric acid, was also identified.

Ether-soluble resin glycosides from the roots of Ipomoea batatas

Two new resin glycosides, batataosides I (1) and II (2), and five known compounds, friedelin (3), scopoletin (4), octadecyl caffeate (5), β-sistosterol (6) and daucosterol (7), were isolated from the roots of Ipomoea batatas. Their structures have been determined based on the chemical and spectral data. Batataosides I and II have novel structures because the core simonic acid B was esterised with cinnamic acid for the first time, and three different substituent esterification groups in one resin glycoside is scarce. The absolute configuration of the aglycone was elucidated to be S by Mosher's method.

Three New Pentasaccharide Resin Glycosides from the Roots of Sweet Potato (Ipomoea batatas)

Three new pentasaccharide resin glycosides, batatosides III-V (1-3), were isolated from the roots of Sweet potato (Ipomoea batatas). Saponification of the crude resin glycoside mixture yielded substituents and simonic acid B. The structures of the isolated compounds (1-3) were established through spectroscopic analyses, including high field NMR spectroscopy and HR-ESI-MS, and chemical correlation. The major characteristics of 3 are the presence of three different substituents, especially the substituent of cinnamic acid was seldom. The monosaccharides of 1-3 were proved by GC-MS and the absolute configuration of aglycone was further established as S by Mosher's method with R-methyloxyphenylacetic acid (MPA) and S-MPA.

Resin Glycosides from Ipomoea pes-caprae

Ipomoea pes-caprae (beach morning-glory; "riñonina" for the herbal drug in Mexico) is prescribed by traditional healers to moderate "heat" in an infected kidney. The hexane-soluble extract from the aerial parts of this medicinal plant, through preparative-scale recycling HPLC, yielded six new lipophilic oligosaccharides of jalapinolic acid: pescaproside B (1) and pescapreins V-IX (2-6). The previously known pescaproside A (7), pescapreins I-IV (8-11), and stoloniferin III (12) were also identified in the analyzed material by means of HPLC comparison with authentic samples. The glycosidic acid structure for all pentasaccharides was confirmed as simonic acid B. Pescaproside B (1), an acylated glycosidic acid methyl ester, is structurally related to pescaprein III (10). Pescapreins V (2) and VI (3) are diasteroisomeric tetraglycosidic lactones of operculinic acid C. Both of these compounds contain (2S)-methylbutyric and n-dodecanoic acids as their esterifying residues. Pescapreins VII (4) and IX (6) are pentasaccharides that contain an n-decanoyl group as their esterifying fatty acid residue instead of the n-dodecanoyl found in pescapreins I (8) and IV (11). Pescaprein VIII (5) represents an isomer of pescaprein II (9) containing an n-dodecanoyl unit as the esterifying residue at position C-4 of the third rhamnose moiety and a 2-methylpropanoyl at C-2 of the second rhamnose. High-field NMR spectroscopy and FAB mass spectrometry were used to characterize all new isolated compounds.

Batatins I and II, Ester-Type Dimers of Acylated Pentasaccharides from the Resin Glycosides of Sweet Potato

Batatins I (1) and II (2), two ester-type dimers of acylated pentasaccharides, have been isolated by recycling HPLC from the hexane-soluble extract of sweet potato (Ipomoea batatas var. batatas). The structures were elucidated by a combination of high-resolution NMR spectroscopy and mass spectrometry. Complete analysis and unambiguous assignments of the 1H and 13C NMR spectra of 1 and 2 were achieved by 2D shift correlation measurements. The glycosidic acid forming each branched pentasaccharide monomeric unit was confirmed as simonic acid B. Three different fatty acids esterify this core at the same positions in both batatins: C-2 on the second rhamnose unit and C-4 and C-2 (or C-3) on the third rhamnose moiety. The acylating residues were identified as (+)-(2S)-methylbutanoic, dodecanoic (lauric), and cinnamic acids. The site of lactonization by the aglycon in unit A was placed at C-3 of the second saccharide. The position for the ester linkage for monomeric unit B on the macrocylic unit A was identified as C-3 of the terminal rhamnose' ''. Through spectroscopic simulation of these complex oligosaccharides, the chemical shifts and coupling constants were deduced for the overlapped proton resonances with a non-first-order resolution. The experimental NMR spectroscopic values registered for batatinoside I (3), a new polyacylated macroyclic pentasaccharide also isolated from this plant, were used as the starting point for spectral simulation of 1 and 2. Both polymers 1 and 2 represent dimers of compound 3.

Resin Glycosides from the Flowers of Ipomoea murucoides

The CHCl(3)-soluble extract from the flowers of the Mexican medicinal plant Ipomoea murucoides, through preparative-scale recycling HPLC, yielded murucoidins I-V (1-5), which are new pentasaccharides of jalapinolic acid, as well as the known stoloniferin I (6). Saponification of the crude resin glycoside mixture yielded two glycosidic acids, simonic acid B (9) and operculinic acid A (10), and their esterifying residues were composed of the two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids. All the isolated compounds (1-6) were characterized through high-field NMR spectroscopy. Compound 4 exhibited marginal cytotoxicity against Hep-2 cells (ED(50) 4 microg/mL).

Characterization of Lipophilic Pentasaccharides from Beach Morning Glory (Ipomoea pes-caprae)

The hexane-soluble extract from the aerial parts of the herbal drug Ipomoea pes-caprae (beach morning-glory), through preparative-scale recycling HPLC, yielded six lipophilic glycosides, namely, five new pentasaccharides of jalapinolic acid, pescaproside A (1) and pescapreins I-IV (2-5), as well as the known stoloniferin III (6). Saponification of the crude resin glycoside mixture yielded simonic acid B (7) as the glycosidic acid component, whereas the esterifying residues of the natural oligosaccharides comprised five fatty acids: 2-methylpropanoic, (2S)-methylbutyric, n-hexanoic, n-decanoic, and n-dodecanoic acids. Pescaproside A (1), an acylated glycosidic acid methyl ester, is related structurally to the product obtained from the macrolactone hydrolysis of pescapreins I-IV (2-5). All the isolated compounds (1-6), characterized through high-field NMR spectroscopy, were found to be weakly cytotoxic to a small panel of cancer cell lines.