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.     

Chaxines B, C, D, and E from the edible mushroom Agrocybe chaxingu

Four novel compounds, chaxines B (1), C (2), D (3), and E (4), were isolated from an edible mushroom Agrocybe chaxingu. The structures of 1-4 were determined by the interpretation of spectroscopic data. Compounds 1 and 2 suppressed the formation of osteoclast.     

Psoracorylifols A-E, five novel compounds with activity against Helicobacter pylori from seeds of Psoralea corylifolia

Five novel compounds, psoracorylifols A-E (1-5) with important activity against Helicobacter pylori have been isolated from a well-known traditional Chinese medicine (TCM), the seeds of Psoralea corylifolia. The structures of compounds 1-5, including their absolute configurations, were established on the basis of spectral methods and biogenetic reason. The structure of 1 was confirmed by a single-crystal X-ray diffraction. Psoracorylifols D and E (4 and 5) represent an unprecedented carbon skeleton. The biogenetic origin of psoracorylifols A-E (1-5) was also postulated.     

The structures of three new shishididemniols from a tunicate of the family Didemnidae

Three new serinolipid derivatives, shishididemniols C (1), D (2), and E (3), were isolated as antibacterial constituents of a tunicate of the family Didemnidae. Their planar structures were elucidated by interpretation of NMR and MS data, whereas the absolute stereochemistry was determined by chemical conversions. Shishididemniols C (3), D (4), and E (5) exhibited antibacterial activity against the fish pathogenic bacterium Vibrio anguillarum.     

Polyketides produced by Daldinia loculata cultured from Northern Manitoba

The fungus present in a soil sample collected from Northern Manitoba was cultured. The natural products produced by this organism were isolated and identified as the polyketides (1), (2), (3). A trace amount of the aromatic alcohol tyrosol (4) was also isolated. This organism was identified as Daldinia loculata by sequencing of the internally transcribed spacer region of the nuclear ribosomal DNA. The polyketides 1-3 were assayed against E. coli and it was observed that 1 displayed mild antibiotic activity.     

Eight new limonoids from Turraea pubescens

Eight new ring B-seco limonoids, turrapubesic acids A-C (1-3) and turrapubesins C-G (4-8), along with turraflorin E and isoazadironolide were isolated from the twigs and leaves of Turraea pubescens. Turrapubesic acids A-C (1-3) are a group of ring B-seco limonoid 17-carboxylic acids with a new C₂₃ skeleton, and turrapubesin C (4) incorporates an unprecedented 1,30-oxygen bridge. The structures including absolute stereochemistry of 1-8 were established on the basis of extensive NMR spectroscopic analysis and CD study. The cytotoxicity of the isolates against the P-388 and A-549 cells was evaluated.     

Separation and identification of three epimeric pairs of new C-glucosyl anthrones from Rumex dentatus by on-line high performance liquid chromatography–circular dichroism analysis

Six C-glucosyl anthrones were characterized as three pairs of epimers by on-line high performance liquid chromatography–circular dichroism (HPLC–CD) analysis and isolated from the roots of Rumex dentatus by column chromatography. Their structures were elucidated by mass spectrometry, nuclear magnetic spectroscopy and HPLC–CD analysis. They are 10R-C-β-d-glucosyl-10-hydroxyemodin-9-anthrone (rumejaposide E, 1) and 10S-C-β-d-glucosyl-10-hydroxyemodin-9-anthrone (rumejaposide F, 2), 10R-C-β-d-glucosylemodin-9-anthrone (rumejaposide G, 3) and 10S-C-β-d-glucosylemodin-9-anthrone (rumejaposide H, 4), 10S-C-β-d-glucosyl-10-hydroxychrysophanol-9-anthrone (cassialoin, 5) and 10R-C-β-d-glucosyl-10-hydroxychrysophanol-9-anthrone (rumejaposide I, 6). Rumejaposides F–I (2–4 and 6) were new C-glucosyl anthrones. Rumejaposide E (1) and cassialoin (5) were isolated for the first time in Rumex plants. On-line HPLC–UV–CD analysis was a useful tool for structure elucidating epimeric C-glycosides anthrones 3–6 because of the poor stability of the pure isomers (3 and 4) and the minute quantity of 5 and 6 in the mixture.     

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.     

Synthesis of branched tri- to pentasaccharides representative of fragments of Shigella flexneri serotypes 3a and/or X O-antigens

Fragments of the {2)-[α-d-Glcp-(1→3)]-α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-[Ac→2]-α-l-Rhap-(1→3)-β-d-GlcpNAc-(1→}_n ((E)AB_AcCD)_n polymer were synthesized. D(E)A, CD(E)A, _AcCD(E)A were obtained according to a linear strategy, whereas BCD(E)A and B_AcCD(E)A were derived from the condensation of appropriate BC and D(E)A building blocks. Oligosaccharides were synthesized as their propyl glycoside, relying on (i) the efficient trichloroacetimidate chemistry, (ii) a common EA allyl glycoside, and (iii) a 2-trichloroacetamido-d-glucopyranose precursor to residue D. Final Pd/C-mediated deprotection, run under a high pressure of hydrogen, ensured O-acetyl stability. All targets are parts of the O-antigen of Shigella flexneri 3a, a prevalent serotype. Non-O-acetylated oligosaccharides are shared by the S. flexneri serotype X O-antigen.     

Absolute stereostructures of inoterpenes A-F from sclerotia of Inonotus obliquus

Six new lanostane-type triterpenes, inoterpenes A (1), B (2), C (3), D (4), E (5), and F (6), were isolated from the sclerotia of Inonotus obliquus together with six known constituents. The chemical structures of new triterpenes 1-6 were characterized on the basis of chemical and physicochemical evidence including the application of the modified Mosher's method.     

Improved synthesis of 1,4-dideoxy-1,4-imino-d-galactitol, an inhibitor of E. coli K12 UDP-Gal mutase and mycobacterial galactan biosynthesis

The E. Coli K12 UDP-Gal mutase inhibitor 1 was prepared from d-glucose in 5 steps (42% overall yield). The 4-azido galactose derivative 11, leading to 1, was formed by treatment of galactose dithioacetal 7 with mercuric oxide and mercuric chloride in acetone. To obtain 7, acetal 3 was tosylated or triflated and treated with NaN₃.     

Daphniglaucins D-H, J, and K, new alkaloids from Daphniphyllum glaucescens

Five new fused-hexacyclic alkaloids, daphniglaucins D (1), E (2), F (3), G (4), and H (5), and two new yuzurimine-type alkaloids, daphniglaucins J (6) and K (7), have been isolated from the leaves of Daphniphyllum glaucescens, and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data and chemical means.     

Seven new alkaloids from the roots of Stemona tuberosa

Seven new alkaloids, named as 1,9-epoxy-9a-hydroxystenine (1), tuberostemoline A (2), tuberostemoline B (3), tuberostemoninol C (4), oxotuberostemonine A (5), the mixture of bisdehydrotuberostemonine D (6), and bisdehydrotuberostemonine E (7), together with four known alkaloids neotuberostemonine (8), sessilifoline B (9), stemoxazolidinone F (10), and tuberostemoninol A (11), were isolated from the roots of Stemona tuberosa. The structures of 1–7 were elucidated through extensive spectroscopic analysis, and the relative configurations of 1–6 and 8 were further confirmed by X-ray crystallographic data. Compounds 8, 9 and the mixture of 6 & 7 exhibited potential acetylcholinesterase (AChE) inhibitory activities.     

Dopamine derivatives from the insect Polyrhachis dives as inhibitors of ROCK1/2 and stimulators of neural stem cell proliferation

Polyrhachis dives is consumed as an insect food in some regions of China. In this study, new dopamine derivatives, (+)-polyrhadopamine A (1a) and (−)-polyrhadopamine A (1b), (+)-polyrhadopamine B (2a) and (−)-polyrhadopamine B (2b), and polyrhadopamines C–E (3–5), were isolated from this species. The structures and stereochemistry of these substances were assigned by using spectroscopic and computational methods. Compounds 1a, 1b, 2a, and 2b are dimeric N-acetyldopamine derivatives, 3 is a dopamine analog containing an unusual sulfone group, and 4 and 5 possess a rare benzo[d]thiazole moiety. The functions of these substances as ROCK1/2 inhibitors, neural stem cell (NSCs) proliferation stimulators, immunosuppressive, and anti-inflammatory agents were determined.     

Synthesis and structural revision of annuionone A

Annuionones (1-5), allelopathic agents isolated from Helianthus annus (sunflower), were reported to be ionone-type bisnorsesquiterepenes. However, the proposed structures for annuionones A (1), B (2) and E (5) were thought to be incorrect. Thus, we have tentatively proposed a revised structure (6) for annuionone A based on careful re-analyses of the reported spectral data. The synthesis of (±)-6 was accomplished to prove the structure of natural annuionone A as 6.     

Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidine

(S)-2-(4-Bromo-2,4′-bithiazole)-1-(tert-butoxycarbonyl)pyrrolidine ((S)-1) was obtained as a single enantiomer and in high yield by means of a two-step modified Hantzsch thiazole synthesis reaction when bromoketone 3 and thioamide (S)-4 were used. Further conversion of (S)-1 into trimethyltin derivative (S)-2 broadens the scope for further cross-coupling reactions.     

Cycloaddition of methyl 2-(2,6-dichorophenyl)-2H-azirine-3-carboxylate to electron-rich 2-azadienes

tert-Butyldimethylsililoxy-2-aza-1,3-butadienes react with 2H-azirine 3 leading to Diels-Alder cycloadducts in moderate yields. The reactions are endo- and regioselective with the azirine being added by its less hindered face. There is only one product in the case of 1b, 4b. There are two isomers (4 and 5) from 1a, 1c and 1d. A different result was obtained with the diene 1e. Diene 1e formed products 4e and 8. Some of compounds 4 and 5 have been hydrolysed leading to functionalised aziridines 7. Compound 8 gave aziridine 9.     

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.     

The enantioselective syntheses of bisabolane sesquiterpenes Lepistirone and Cheimonophyllon E

The synthetic approach to the bisabolane sesquiterpenes Lepistirone 1 and Cheimonophyllon E 2 involves the transformation of (+)-2-carene (5) into the p-menthane furans 8 and 11. Regio- and stereoselective alkylation, and standard reactions complete the enantioselective syntheses.     

Shearinines D-K, new indole triterpenoids from an endophytic Penicillium sp. (strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels

A chemical examination of the endophytic fungus Penicillium sp. isolated from the mangrove plant Aegiceras corniculatum resulted in the isolation and characterization of eight new indole triterpenes named shearinines D-K (1-8), along with shearinine A (9), paspalitrem A (10), and paspaline (11). Their stereostructures were determined by extensive spectroscopic data analyses and quantum chemical circular dichroism calculations. The biosynthetic relationship of all 11 alkaloids is suggested. Shearinines D (1), E (2), and (with reduced potency) G (4) exhibit significant in vitro blocking activity on large-conductance calcium-activated potassium channels.