Total synthesis and biological evaluation of tamandarin B analogues

Tamandarins A and B are a class of marine natural cyclodepsipeptides with structures and biological activities closely related to those of the didemnins. The easier synthetic access to tamandarins accelerates the preparation of new macrocyclic derivatives of this family of antitumor, antiviral, and immunosuppressive compounds. The optimization of the previously reported synthetic route to tamandarins by changing the macrolactamization site from Nst1 and Thr6 to Pro4 and N,O-Me2Tyr5 residues led to a significant improvement in the reaction yield. Using this new synthetic approach, four new macrocyclic analogues of tamandarin B were prepared and evaluated for anticancer activity. These results provide further insight into the structure-activity relationship of the tamandarins and didemnins.     

Total syntheses and biological investigations of tamandarins A and B and tamandarin A analogs.

Tamandarins A (1) and B (2), two natural products similar in structure to didemnin B (3), were recently isolated from a Brazilian marine ascidian of the family Didemnidae. The cytotoxicity of 1 was reported to be somewhat more potent in vitro than that of 3 against various human cancer cell lines. The present account describes the first total syntheses of 1 and 2, and the syntheses of tamandarin A side chain analogues. The cytotoxicity data for these compounds show that the side chain modifications exhibit a parallel effect for both didemnins and tamandarins. This observation supports tamandarins' role as didemnins' mimic.     

Structural determination of silymins A and B, new pentacyclic triterpenes from Silybum marianum, by 1D and 2D NMR spectroscopy

Silymins A (1) and B (2), the new pentacyclic triterpenes, have been isolated from ethyl acetate fraction of Silybum marianum and their structures assigned from 1H and 13C NMR spectra, DEPT and by 2D COSY, NOE and HMBC experiments.     

Isolation and structural determination of sorbinols A and B, new triterpenes from Sorbus cashmariana, by 1D and 2D NMR spectroscopy

Two new pentacyclic triterpenes, sorbinols A (1) and B (2) have been isolated from the ethyl acetate fraction of Sorbus cashmariana and their structures assigned from (1)H and (13)C NMR spectra, DEPT and by 2D COSY, NOE, HMQC and HMBC experiments. Both 1 and 2 showed moderate inhibitory potential against the enzyme lipoxygenase.     

Chejuenolides A and B, new macrocyclic tetraenes from the marine bacterium Hahella chejuensis

Two new 17-membered carbocyclic tetraenes, chejuenolides A and B (1 and 2), have been isolated from the EtOAc extract of the marine bacterium Hahella chejuensis by various chromatographic methods. The structures and relative configurations of 1 and 2 were mainly determined by analysis of the NMR spectroscopic data, and their absolute configurations were assigned by application of modified Mosher method.     

Dichotomains A and B: two new highly oxygenated phenolic derivatives from Dicranopteris dichotoma

[structure: see text] Dichotomains A (1) and B (2), two new highly oxygenated phenolic derivatives that feature a spirodilactone moiety in their structures, were isolated from the fronds of Dicranopteris dichotoma. Their structures were elucidated on the basis of NMR and MS spectroscopic data, and the stereochemistry of 1 was finally determined by single-crystal X-ray diffraction. Compound 2 showed weak anti-HIV-1 activity.     

Two new polyketides from Hawaiian endophytic fungus Pestalotiopsis sp. FT172

Two new polyketides, pestalotiotones A (1) and B (2) were isolated from the cultured broth of Pestalotiopsis sp. FT172. The structures of compounds 1 and 2 were determined by analysis of HRMS and NMR spectroscopic data. The absolute configurations of compound 1 were assigned by Mosher reaction, J-based configuration analysis, and DP4 NMR calculations. Both compounds were tested against cancer cell lines, pathogenic fungi and bacteria.     

Two new C-glycosylflavones from the leaves of Iris lactea var.chinensis

Two new acylated C-glycosylflavones were isolated from the leaves of Iris lactea var. chinensis, and their structures were elucidated on the basis of extensive NMR experiments and mass spectrometry methods and were assigned as 5-hydroxy-4＇- methoxyflavone-7-O-（β-D-2＇＇＇＇4＇＇＇＇-diacetylrhamnopyranosyl）-6-C-[ O-（α-L-6＇＇＇-acetyl-glucpyranosyl）-1→2-β-D-glucopyrano- side] （irislactin A） and 5-hydroxy-4＇,7-dimethoxyflavone-6-C-[O-（α-L-2＇＇＇,3＇＇＇-diacetylrhanmo-pyranosyl）-1→ 2-β-D-glucopyranoside] （irislactin B）.     

A simple microscale method for determining the relative stereochemistry of statine units

A simple method to determine the relative stereochemistry of statine amino acids (gamma-amino-beta-hydroxyacids) by using (1)H NMR spectroscopy is described. Configurational assignment of statine units within complex natural products is possible without degradation or derivatization as the syn and anti diastereomers can be distinguished by using a combination of chemical shift and coupling constant information derived from the alpha-methylene ABX system. Seventy-three examples are provided, demonstrating the scope and limitations of the methodology. These examples range in complexity from simple statine units to cyclic depsipeptides, such as tamandarin B.     

New Stephaoxocane Alkaloids from Stephania longa

Three new stephaoxocane‐type alkaloids, stephalonganines A–C ( 1 – 3 ), together with the known eletefine ( 4 ), were isolated from the whole plant of Stephania longa. Their structures were fully characterized spectroscopically, and the absolute configurations of the new alkaloids were assigned by comparison of their circular‐dichroism (CD) data with those of 1,2‐dihydrostephaoxocanine ( 5 ), in combination with 2D‐NMR experiments.     

A Pair of New Nortriterpene Saponin Epimers from the Roots of Gypsophila oldhamiana

A pair of new oleanane‐type nortriterpene saponin epimers, neogypsoside A ( 1 ) and B ( 2) (Fig. 1) with neogypsogenin A ( 3 ) and neogypsogenin B ( 4 ) as the two new aglycons, as well as the two known triterpene saponins 5 and 6 (Fig. 1), were isolated from the roots of Gypsophila oldhamiana. Their structures were determined by analysis of their NMR data. A possible biogenetic pathway to the nortriterpene saponins 1 and 2 is proposed (Scheme 2).     

Two new eremophilenolides from the roots of Ligulariopsis shichuana and their anti-phytopathogenic fungal and antifeedant activities

Two new eremophilenolides, ligushicins A (1) and B (2), and two known compounds including β-sitosterol and ursolic acid were isolated from Ligulariopsis shichuana. The structures of new compounds were established on the basis of 1D and 2D NMR data and HRESIMS data interpretation. The absolute configuration of new compounds was assigned by ECD spectroscopy, and that of ligushicins A (1) was confirmed by X-ray diffraction analysis. The antifungal and antifeedant activities of new compounds were evaluated against four plant pathogenic fungi and third-instar larvae of Plutella xylostella, respectively. Ligushicins A (1) and B (2) exhibited potent antifungal activity against Botrytis cinerea and Fusarium oxysporum with minimum inhibitory concentration (MIC) values ranging from 50 to 100 mg/L, while they also exhibited weak antifeedant activities.     

Structural determination of salsolins A and B, new antioxidant polyoxygenated triterpenes from Salsola baryosma, by 1D and 2D NMR spectroscopy

Salsolins A (1) and B (2), the new triterpenes, have been isolated from the chloroform soluble fraction of Salsola baryosma along with 2alpha,3beta,23,24-tetrahydroxyurs-12-en-28-oic acid (3) reported for the first time from this species. Their structures have been assigned from 1H and 13C NMR spectra, DEPT and by 2D COSY, NOESY, HMQC and HMBC experiments. The compounds 1-3 showed significant antioxidant activity.     

Scytalidamides A and B, new cytotoxic cyclic heptapeptides from a marine fungus of the genus Scytalidium

Two new cyclic heptapeptides have been isolated from the culture broth of a marine fungus, Scytalidium sp., collected from the Bahamas. The planar structures of scytalidamides A (1) and B (2) were assigned on the basis of 1D and 2D NMR spectroscopic techniques, while the absolute configuration of the amino acid residues in both molecules was determined by application of the advanced Marfey's method. The absolute stereochemistry of the uncommon 3-methylproline moiety in scytalidamide B (2) was confirmed by isolation and CD measurements, as well as application of the advanced Marfey's method. Scytalidamides A (1) and B (2) showed moderate in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC(50) values of 2.7 and 11.0 microM, respectively.     

5-Alkylpyrrole-2-carboxaldehyde derivatives from the Chinese sponge Mycale lissochela and their PTP1B inhibitory activities

Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15(1) and mycalenitrile-16(2),along with five known related ones(3-7),were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB(Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity) inhibitory activities with IC_(50) values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.     

Salvinicins A and B, new neoclerodane diterpenes from Salvia divinorum

[reaction: see text] Two new neoclerodane diterpenes, salvinicins A (4) and B (5), were isolated from the dried leaves of Salvia divinorum. The structures of these compounds were elucidated by spectroscopic techniques, including (1)H and (13)C NMR, NOESY, HMQC, and HMBC. The absolute stereochemistry of these compounds was assigned on the basis of single-crystal X-ray crystallographic analysis of salvinicin A (4) and a 3,4-dichlorobenzoate derivative of salvinorin B.     

Three new cycloartane triterpene glycosides from Souliea vaginata

Three new cycloartane triterpene glycosides, soulieosides A (1), B (2), and C (3), were isolated from the rhizomes of Souliea vaginata, and their structures were elucidated on the basis of extensive NMR experiments and chemical methods. Soulieosides A-C were assigned as 25-O-acetylcimigenol-3-O-beta-D-(2-acetyl)xylopyranoside (1), 24-O-acetyl-isodahurinol-3-O-beta-D-(2-acetyl)xylopyranoside (2) and 20(S),22(R),23(S),24(R)-16beta:23;22:25-diepoxy-3beta,23,24-trihydroxy-9,19-cyclolanostane-3-O-beta-D-(4-acetyl)xylopyranoside (3), respectively.     

Complete assignments of (1)H and (13)C NMR spectroscopic data for two new triterpenoid saponins from Ilex pernyi

Ilexpernoside A and ilexpernoside B, two new pentacyclic C(4)-nortriterpenoid saponins, were isolated from the leaves of Ilex pernyi Franch. Their chemical structures were determined by MS, NMR spectroscopy and chemical analysis. Complete assignments of the (1)H and (13)C NMR spectroscopic data were achieved by 1D and 2D NMR experiments (HSQC, HMBC, (1)H-(1)H COSY and NOESY).     

Three minor new compounds from the aerial parts of Leonurus japonicus

Phytochemical investigation of the aerial parts of Leonurus japonicus led to the isolation of one new labdane diterpenoid, leojaponin D(1) and two new ionone derivatives, leojaponones A and B(2 and 3),together with seven known diterpenoids(4–10). Their structures were elucidated by extensive 1D and2 D NMR spectroscopic data and by comparison with data reported in the literature. Selected isolates were evaluated their effects on Jurkat IL2 secretion.     

New cytotoxic apigenin derivatives from Selaginella doederleinii

75%aqueous ethanol extract from the whole herbs of Selaginella doederleinii was isolated,and two new apigenin derivatives,doederflavones A(1) and B(2),together with ten known compounds(3-12) were characterized.Their structures were assigned by extensive spectroscopic methods including 1D/2D NMR and HR-ESIMS.Compounds 1-6 bear an aryl substituent at the C-8 or C-6 positions in ring A of apigenin skeleton.Compounds 1 and 2 were evaluated for their in vitro cytotoxicity against four human cancer cell lines A549,MCF-7,SMMC-7721,and LoVo,both of which exhibited significant cytotoxicity against A549 with IC_(50) values of 0.82 μmol/L and 1.32 μmol/L,respectively.