Five novel norcembranoids from Sinularia leptoclados and S. parva

Three new norcembrane-based diterpenoids, leptocladolides A (1), B (4) and C (5), along with five known metabolites 6-10, have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados. Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1-epi-leptocladolide A (2) and 7E-leptocladolide A (3), in addition to 1 and 7. The structures of new metabolites 1-5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.     

Briaexcavatins C-F, four new briarane-related diterpenoids from the Formosan octocoral Briareum excavatum (Briareidae)

Four new briarane-related diterpenoids, designated as briaexcavatins C-F (1-4), were isolated from the Formosan octocoral Briareum excavatum, collected off southern Taiwan coast. The structures of these new metabolites were elucidated by the interpretation of spectroscopic and chemical methods. The configuration of 1 was further supported by molecular mechanics calculations. Briarane 1 has been shown to exhibit mild cytotoxicity toward MDA-MB-231 human breast tumor cells and briarane 3 was found to show activity to inhibit neutrophil elastase release in humans.     

Briaexcavatolides X-Z, three new briarane-related derivatives from the gorgonian coral Briareum excavatum

Three new polyoxygenated briarane-type diterpenoids, briaexcavatolides X-Z (1-3), have been isolated from the gorgonian coral Briareum excavatum. The structures, including the relative configurations of briaranes 1-3, were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The configuration of briarane 1 was further supported by molecular mechanics calculations.     

Structure of seven new vibsane-type diterpenoids from Viburnum awabuki

Seven new vibsane-type diterpenoids, 6-O-methyl-6,7-dihydroxyvibsanin B (1), 4-hydroxyvibsanin A (2), 14(R*),15-epoxyneovibsanin B (3), 14(S*),15-epoxyneovibsanin B (4), (8Z)-neovibsanin B (5), 18-O-methylvibsanin C (6), and (8Z)-vibsanin E (7), have been isolated from the leaves of Viburnum awabuki. Their structures have been elucidated by molecular mechanics 2 (MM2) calculations and comparison of the spectroscopic data, including ¹³C NMR data, with those of previously known compounds. Moreover, neovibsane-type diterpenoids 3, 4, and 5 enhanced the neurite outgrowth of NGF-mediated PC12 cells at a concentration of 40 μM.     

Cytotoxic sesquiterpenes from luminescent mushroom Neonothopanus nambi

Four new aristolane sesquiterpenes named nambinones A–C (1–3) and 1-epi-nambinone B (4), a new sesquiterpene, nambinone D (5), a known compound, aurisin A (6) as well as a new dimeric sesquiterpene, aurisin K (7), were isolated from two isolates of luminescent mushroom, Neonothopanus nambi, PW1 and PW2. These structures were established on the basis of spectroscopic evidence. The relative configuration of 6 was determined by X-ray crystallographic analysis. Compounds 6 and 7 exhibited antimalarial activity against Plasmodium falciparum and antimycobacterial activity against Mycobacterium tuberculosis. Compounds 3, 6, and 7 showed cytotoxicity against NCI-H187 cancer cell lines. In addition, 6 and 7 showed cytotoxicity against the cholangiocarcinoma cell lines.     

Dichotellides A-E, five new iodine-containing briarane type diterpenoids from Dichotella gemmacea

Five new briarane type diterpenoids, dichotellides A−E (1−5), were isolated from the South China Sea gorgonian Dichotella gemmacea together with four known analogues (6−9). Compounds 1−5 represent the first examples of iodine-containing briarane type diterpenoids from nature. The structures of these diterpenoids were elucidated by spectroscopic analysis, including 1D, 2D-NMR, and HRESIMS, and the absolute configuration of 1 was further confirmed by single crystal X-ray diffraction analysis. All the isolates were evaluated for cytotoxicity activity against four human tumor cell lines, and only 3 exhibited marginal activity against SW1990 (human pancreatic cancer).     

Lanostane triterpenoids from the edible mushroom Astraeus asiaticus

Seven new lanostane triterpenoids, astraeusins M–Q (1–5), 26-epi-artabotryol C1 (6), and 26-epi-astrasiaone (7), together with seventeen known compounds (8–24), were isolated from the food mushroom Astraeus asiaticus. The C-26 configuration of artabotriol C1 and astrasiaone, originally reported as 26R (6 and 7, respectively), was revised to be 26S (16 and 17, respectively). Astraeusin M (1) exhibited antimalarial activity against Plasmodium falciparum K1 with an IC₅₀ value of 3.0 μg/mL.     

New briaranes from the octocorals Briareum excavatum (Briareidae) and Junceella fragilis (Ellisellidae)

Six 12-hydroxybriaranes, including four new diterpenoids, briaexcavatins I-L (1-4), and two known metabolites, excavatolides C (5) and E (6), have been isolated from the cultured scleraxonia Briareum excavatum. In addition, the gorgonian coral Junceella fragilis yielded a new chlorinated briarane, fragilide C (10). The structures of above compounds were determined by spectroscopic methods and the structures of 5 and 6 were further confirmed by X-ray data analysis for the first time. The absolute configuration of 6 was elucidated by chemical conversion. Some of these briaranes have displayed inhibitory effects on superoxide anion generation by human neutrophils.     

Sartorymensin,a new indole alkaloid,and new analogues of tryptoquivaline and fiscalins produced by Neosartorya siamensis (KUFC 6349)

Seven new indole alkaloids including a new indoloazepinone derivative (2), two new quinazolinone derivatives (7, 8) and four new pyrazinoquinazolinone derivatives: epi-fiscalin C (10), epi-fiscalin A (12), neofiscalin A (13), epi-neofiscalin A (14) were isolated, together with 4-dihydroxy-3-methylacetophenone (1), tryptoquivaline (3), tryptoquivalines L (4), H (5), F (6) as well as fiscalins A (11) and C (9), from the culture of the fungus Neosartorya siamensis (KUFC 6349). The absolute configuration of the stereogenic carbons of the previously reported tryptoquivalines F, H, L was revised using the data obtained from an X-ray analysis of tryptoquivaline l and the NOESY correlations. The structures of the new pyrazinoquinazolinone derivatives (10, 12, 13, 14) were established based on 1D and 2D NMR spectral analysis, and the absolute configuration of their stereogenic carbons was determined by an X-ray crystallographic analysis of fiscalin C (9) and a new compound epi-fiscalin C (10), in conjunction with the correlations observed in their NOESY and long range COSY spectra. Compounds 2–8 and 12 were evaluated for their in vitro growth inhibitory activity on the human U373 and Hs683 glioblastoma, the A549 non-small cell lung cancer, the MCF-7 breast cancer and the SKMEL-28 melanoma cell lines by MTT colorimetric assay.     

Three new diterpenoids, tricalysiolide H and tricalysiones A and B, from Tricalysia dubia

Three new diterpenoids, tricalysiolide H (1) and tricalysiones A (2) and B (3), with novel structural features were isolated from the wood of Tricalysia dubia, together with a known compound, cafestol (4). The structures of 1-3 were elucidated on the basis of 2D NMR spectroscopy and X-ray crystallographic analysis.     

Ten new antifouling briarane diterpenoids from the South China Sea gorgonian Junceella juncea

Ten new antifouling briarane diterpenoids, juncins R-ZI (1-10) were isolated from the South China Sea gorgonian coral Junceella juncea. The structures of these new compounds were established by extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1-10 all showed potent antifouling activities against the larval settlement of barnacle Balanus amphitrite at nontoxic concentrations with EC₅₀ values of 0.004, 0.34, 2.65, 1.61, 3.77, 21.06, 0.004, 0.14, 1.47, and 0.51 μg mL⁻¹. The structure-activity relationship was discussed.     

Total Synthesis of Amphidinolide E and Amphidinolide E Stereoisomers

Four amphidinolide E stereoisomers, amphidinolide E (1), 2-epi-amphidinolide E (2), 19-epi-amphidinolide E (3), and 2-epi-19-epi-amphidinolide E (4), have been synthesized via the judicious union of aldehyde 5, allylsilanes 7 or 8, acids 9 or 10, and vinylstannane 6. The C19 stereocenters of the C19 epimeric allylsilanes 7 and 8 were introduced via crotylboration reactions early in the synthesis. [3+2] Annulation reactions of aldehyde 5 with allylsilanes 7 and 8 were employed to set the core tetrahydrofuran units of 1-4. Finally, the C2 stereocenter was installed by esterification using acid 9, without incident, or with acid 10, in which case an unexpected and completely stereoselective inversion of C2 occurs.     

Synthesis and evaluation of 1-deoxy-8-epi-castanospermine, 1-deoxy-8-hydroxymethyl castanospermine, and (6S,7S,8R,8aR)-8-amino-octahydroindolizine-6,7-diol

A short, versatile, and enantioselective synthesis of 1-deoxy-8-epi-castanospermine (5), 1-deoxy-8-hydroxymethyl castanospermine (6), and (6S,7S,8R,8aR)-8-amino-octahydroindolizine-6,7-diol (7) is achieved from a common template 12. The key step utilized is PET provoked amine radical cyclization of 11 to 12 in excellent diastereoselectivity. The exocyclic double bond at C-8 of the template is functionalized to obtain 5-7 as exclusive diastereomers. 1-Deoxy-8-epi-castanospermine exhibited inhibition of α- and β-galactosidase and β-glucosidase. Compounds 6 and 7 were found to be weak inhibitors of β-glucosidase.     

Bis-spiro-azaphilones and azaphilones from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05

Four new dimeric spiro-azaplilones, cochliodones A-D (1-4), two new azaphliones, chaetoviridines E and F (5 and 6), a new epi-chaetoviridin A (7), together with five known compounds, chaetoviridin A (8), ergosterol (9), chaetochalasin A (10), 24(R)-5α,8α-epidioxyergosta-6-22-diene-3β-ol (11), and ergosterol-β-d-glucoside (12) were isolated from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05. Structures and stereochemistry of the atropisomers 1-3 were determined by single-crystal X-ray diffraction analysis. Compounds 5, 10, and 11 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, 6, 10, and 11 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, 5 and 6 also showed cytotoxicity against the KB, BC1, and NCI-H187 cell lines.     

In vivo transformations of dihydro-epi-deoxyarteannuin B in Artemisia annua plants

[15-¹³C²H₃]-dihydro-epi-deoxyarteannuin B (4a) has been fed to intact Artemisia annua plants via the root and three labeled metabolites (17a-19a) have been identified by 1D- and 2D-NMR spectroscopies. The in vivo transformations of 4a in A. annua are proposed to involve enzymatically-mediated processes in addition to possible spontaneous autoxidation. In the hypothetical spontaneous autoxidation pathway, the tri-substituted double bond in 4a appears to have undergone ‘ene-type’ reaction with oxygen to form an allylic hydroperoxide, which subsequently rearranges to the allylic hydroxyl group in the metabolite 3α-hydroxy-dihydro-epi-deoxyarteannuin B (17a). In the enzymatically-mediated pathways, compound 17a has then been converted to its acetyl derivative, 3α-acetoxy-dihydro-epi-deoxyarteannuin B (18a), while oxidation of 4a at the ‘unactivated’ 9-position has yielded 9β-hydroxy-dihydro-epi-deoxyarteannuin B (19a). Although all of the natural products artemisinin (1), arteannuin K (7), arteannuin L (8), and arteannuin M (9) have been suggested previously as hypothetical metabolites from dihydro-epi-deoxyarteannuin B in A. annua, none were isolated in labeled form in this study. It is argued that the nature of the transformations undergone by compound 4a are more consistent with a degradative metabolism, designed to eliminate this compound from the plant, rather than with a role as a late precursor in the biosynthesis of artemisinin or other natural products from A. annua.     

New xenicane diterpenoids from Xenia florida

Three new xenicane diterpenoids, designated xeniolactones A (1), B (2), and C (3), were isolated from Xenia florida collected in Taiwan. Compound 1 possesses a novel structure having a heterotricyclic skeleton in cyclononane system. The structures of 1-3 were elucidated on the basis of extensive spectroscopic analysis. The cytotoxicity of 1-3 was also evaluated against human cancer cell lines.     

A new eudesmane sesquiterpene glycoside from Parepigynum funingense

A new eudesmane sesquiterpene glycoside,1α,6β-dihydroxy-5,10-bis-epi-eudesm-4(15)-ene-6-O-β-D-glucopyranoside(2), together with a known analogue compound,1α,6β-dihydroxy-5,10-bis-epi-eudesm-3-ene-6-O-β-D-glucopyranoside(1),were isolated from the roots of Parepigynumfuningense.The structure of 2 was determined by 1D and 2D NMR spectroscopy.Compound 1 was isolated from this plant for the first time.     

Synthesis of nor-sesquiterpene spirolactones and their steroidal hybrids revisited. The neopentyl dilemma: misassignment of one stereocentre may necessitate a completely new approach

Inversion at the highly congested C1 position of 1-epi-pathylactone A (1-epi-1), or its corresponding steroidal hybrid 8a, using a diverse range of published procedures including microwave assisted Mitsunobu reaction or via oxidation to the corresponding ketone and subsequent reduction, was unsuccessful in our hands. Attempts to convert the C1 hydroxyl group into its corresponding chloride, en route to napalilactone 2a, also failed. Precursors with the C1α configuration installed at early stage proved not to be amenable to the targets under a broad range of conditions.     

8-epi-erythronolide B and its metabolic fate in fermentations of Streptomyces erythreus

8-epi-erythronolide B (4) has been isolated as a product formed from the acid treatment of erythronolide B (3). When this compound was fed to a blocked mutant of the erythromycin producing organism, Streptomycetes erythreus (Abbott 2NU153), nearly quantitative yields of 3-O-(α-l-mycarosyl)-8-epi-erythronolide B (10) were obtained. The much desired 8-epi-erythromycins (2) were not realized.     

Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus,Gibellula formosana,cultivated in the presence of epigenetic modifying agents

The concomitant addition of a histone deacetylase inhibitor, suberoyl bis-hydroxamic acid, and a DNA methyltransferase inhibitor, RG-108, to the culture medium of Gibellula formosana, an entomopathogenic fungus, induced a significant increase in diversity of secondary metabolites. From the culture media were isolated two new highly oxidized ergosterols, formosterols A (1) and B (2), and five new isariotin analogs, 12′-O-acetylisariotin A (4), 1-epi-isariotin A (5), and isariotins K–M (6–8), together with 22,23-epoxy-3,12,14,16-tetrahydroxyergosta-5,7-dien-11-one (named formosterol C) (3), isariotins A (9), C (10), and E (11), TK-57-164A (12), and beauvericin (13). The NMR spectra, X-ray single crystallographic diffraction, and chemical transformations revealed the structures of the two new formosterols and five new isariotins. The stereochemistry of formosterol C (3) was deduced from its spectroscopic data. The side chains of formosterols A–C (1–3) contained cis-22,23-epoxide, which is rarely present in naturally occurring sterols and triterpenes.