Three New, 1‐Oxygenated ent‐8,9‐Secokaurane Diterpenes from Croton kongensis

Three new ent‐8,9‐secokaurane diterpenes, kongensins A–C ( 1 – 3 ), were isolated from the aerial parts of Croton kongensis, together with two known compounds, rabdoumbrosanin ( 4 ) and (7α,14β)‐7,14‐dihydroxy‐ent‐kaur‐16‐en‐15‐one ( 5 ). The structures of the new compounds were elucidated by HR‐MS as well as in‐depth 1D‐ and 2D‐NMR analyses. Compounds 1 – 3 showed an unusual oxygenation pattern, with an AcO or OH group at C(1), in combination with a Δ⁸⁽¹⁴⁾ unsaturation ( 1 ) or an 8,14‐epoxide function ( 2, 3 ).     

Two New Steroidal Alkaloids from Veratrum nigrum L.

Phytochemical studies on Veratrum nigrum L., collected in Shanxi, P. R. China, resulted in the isolation of two new steroidal alkaloids, 23‐methoxycyclopamine ( 1 ) and 15‐O‐(2‐methylbutanoyl)‐3‐O‐veratroylprotoverine ( 2 ). The structures of the two new compounds were established by means of extensive NMR spectroscopic studies.     

Dioxopiperazine Alkaloids Produced by the Marine Mangrove Derived Endophytic Fungus Eurotium rubrum

Cultivation of the fungal strain Eurotium rubrum, an endophytic fungus that was isolated from the inner tissue of stems of the mangrove plant Hibiscus tiliaceus, resulted in the isolation of two new dioxopiperazine derivatives, namely, dehydrovariecolorin L ( 1 ) and dehydroechinulin ( 2 ), together with eight known dioxopiperazine compounds including variecolorin L ( 3 ), echinulin ( 4 ), isoechinulin A ( 5 ), dihydroxyisoechinulin A ( 6 ), preechinulin ( 7 ), neoechinulin A ( 8 ), neoechinulin E ( 9 ), and cryptoechinuline D ( 10 ). The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature. Compounds 1, 2, 9 , and 10 were investigated for their α,α‐diphenyl‐β‐picrylhydrazyl (DPPH) radical‐scavenging activity. In addition, the new compounds, 1 and 2 , were evaluated for their cytotoxic activity against the P‐388, HL‐60, and A549 cell lines.     

Complex Polypropionates from a South China Sea Photosynthetic Mollusk: Isolation and Biomimetic Synthesis Highlighting Novel Rearrangements

Placobranchus ocellatus is well known to produce diverse and complex γ‐pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A–D, a series of racemic non‐γ‐pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane ( 1 , 2 ), a bicyclo[3.3.1]nonane ( 3 ) or a mesitylene‐substituted dimethylfuran‐3(2H)‐one core ( 4 ). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X‐ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1 – 4 after chiral HPLC resolution. An array of new and diversity‐generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co‐occurring γ‐pyrones ( 5 – 10 ). Furthermore, the successful biomimetic semisynthesis of ocellatusone A ( 1 ) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction.     

Cytotoxic Constituents of Piper sintenense

A new pyridone alkaloid, 5,6‐dihydro‐5‐hydroxy‐1H‐pyridin‐2‐one ( 1 ), and a new ester, sintenin (=3‐(3,4‐dimethoxyphenyl)propyl 3‐(3,4‐dimethoxyphenyl)propanoate 2 ), together with three known compounds, 5,6‐dihydro‐1H‐pyridin‐2‐one ( 3 ), d‐sesamin (=5,5′‐(3a,4,6,6a‐tetrahydro‐1H,3H‐furo[3,4‐c]furan‐1,4‐diyl)bis[1,3‐benzodioxole]; 4 ), and (E)‐phytol (=3,7,11,15‐tetramethylhexadec‐2‐en‐1‐ol; 5 ) have been isolated from the whole plant of Piper sintenense. The structures of the two new compounds were determined through spectral analyses. Among twenty isolates obtained so far, four compounds exhibited effective cytotoxicities against P‐388, HT‐29, or A549 cell lines in vitro.     

π‐Excess Aromatic σ2P Ligands: Formation of a Heterocyclic 1,2‐Diphosphine by the Addition of tBuLi and Subsequent Inverse Addition of the Product at the P=C Bonds of Two Molecules of 1‐Neopentyl‐1,3‐benzazaphosphole

The reactivity of tBuLi (pentane) toward the N‐neopentyl‐substituted π‐excess P=CH–N heterocycle 1 depends on the solvent (tetrahydrofuran, diethyl ether, hexane, and toluene) and reaction conditions. Trapping of the resulting organolithium compounds with CO₂/ClSiMe₃, ClSiMe₃, or EtI led to various products indicating CH lithiation ( 1a , b ), normal addition of tBuLi at the P=C bond (E/Z ‐2a , b ), inverse addition of the primary addition product 2_Li at the P=C bond of a second molecule 1 , affording 3‐tert‐butyl‐2,2’‐bis(1,3‐benzazaphospholines) 3 , or inverse addition of tBuLi ( 4b,c ). The formation of 3 demonstrates a novel route to asymmetric heterocyclic 1,2‐diphosphine ligands. The structure elucidation of the new compounds is based on their ³¹P and ¹³C NMR data with conclusive chemical shifts and P–C coupling constants, that of the isolated PH‐functionalized diphosphine 3 on crystal structure analysis.     

Cytotoxic Withaphysalins from Physalis minima

A novel withanolide, withaphysalin P ( 1 ) with a nine‐membered ring, and six other new withaphysalins, 2 – 7 , together with the three known withaphysalins 8 – 10 were isolated from Physalis minima L. The structures were deduced by means of spectroscopic analyses, and that of withaphysalin P ( 1 ) was confirmed by a single‐crystal X‐ray diffraction analysis. Plausible biosynthetic pathways were postulated (Scheme 1). All compounds were tested for their antiproliferative activities toward the human colorectal‐carcinoma HCT‐116 cells and human nonsmall‐cell lung‐cancer NCI‐H460 cells (Table 4). Compounds 1 – 3, 7 – 10, 7a , and 7b displayed moderate cytotoxic activity against the two human cancer cell lines.     

Structure‐Based Design of Nonpeptidic Thrombin Inhibitors: Exploring the D‐Pocket and the Oxyanion Hole

Structure‐activity relationships for new members of a class of nonpeptidic, low‐molecular‐weight inhibitors of thrombin, a key serine protease in the blood coagulation cascade, are described. These compounds, which originate from X‐ray‐structure‐based design, feature a conformationally rigid, bi‐ or tricyclic core from which side chains diverge into the four major binding pockets (distal D, proximal P, recognition or specificity S1, and oxyanion hole O) at the thrombin active site (Fig. 1). Phenylamidinium is the side chain of choice for the S1 pocket, while the most active inhibitors orient an i‐Pr group into the P‐pocket (Table 1). The key step in the synthesis of the inhibitors is the construction of the central bi‐ or tricyclic scaffold by 1,3‐dipolar cycloaddition of an in situ prepared azomethine ylide and an N‐substituted maleimide (Schemes 1–3, and 8–10). One series of compounds was designed to explore the binding features of the large hydrophobic D pocket. This pocket provides space for lipophilic residues as bulky as benzhydryl groups. A new strategy was developed, allowing introduction of these sterically demanding substituents very late in the synthesis (Schemes 5 and 6). Benzhydryl derivative (±)‐ 2 was found to be the most selective member (K_i (trypsin)/K_i (thrombin)=1200) of this class of nonpeptidic thrombin inhibitors, while the ‘dipiperonyl' analog (±)‐ 3 (K_i=9 nM , 7.60‐fold selectivity) displays the highest potency of all compounds prepared so far (Table 1). A second series of inhibitors features side chains designed to orient into the oxyanion hole and to undergo H‐bonding with the backbone NH groups lining the catalytic site of the enzyme. Unfortunately, neither activity nor selectivity could be substantially improved by introduction of these substituents (Table 2). Presumably, the high degree of pre‐organization and the rigidity of the tightly bound scaffolds prevents the new substituents from assuming a position that would allow favorable interactions in the oxyanion hole. However, the oxyanion hole and the S1′ pocket next to it were found to be capable of accommodating quite large groups, which leaves much room for further exploration.     

Palaeophytochemical Components from the Miocene‐Fossil Wood of Pinus Griffithii

Some Miocene‐fossil wood of Pinus griffithii preserved as lignified wood in brown coal was found in an open coalmine in Xundian of Yunnan Province, China. To explore its chemical components, here we show the palaeophytochemical investigation of this Pliocene‐fossil wood of P. armandii, resulting in the isolation of 11 compounds ( 1–11 ) including one new compound named 3,3‐dimethoxy‐24‐ethyl‐cholestan ( 1 ) by liquid column chromatography. Furthermore, sixteen volatiles were detected from this fossil wood by gas chromatography‐mass spectrometry (GC‐MS). These structures of 11 compounds were elucidated by analysis of their MS, 1D and 2D‐NMR spectra, and comparison with published data.     

Tasumatrols P – T,Five New Taxoids from Taxus sumatrana

The phytochemical investigation of the more polar fractions from the leaves and twigs of Taxus sumatrana (Taxaceae) afforded five new taxane diterpene esters, tasumatrols P–T ( 1 – 5 ) possessing an 11(15→1),11(10→9)‐diabeotaxane skeleton. Compounds 1, 4 , and 5 contain an α‐hydroxy group at C(14), while 3 has no OH group at either C(13) or C(14). Compound 2 is a natural 4,5‐acetonide derivative, while 4 has an unusual spiro‐connected 2‐hydroxy‐2‐phenyl‐1,3‐dioxolane ring. Ten known taxoids, were also isolated in the course of the chromatographic fractionation. Five additional new O‐acetyl derivatives 3a, 4a, 4b, 5a , and 5b were prepared from the taxanes 3 – 5 . The structures of all new compounds were established on the basis of their spectroscopic analyses. Compound 1 showed mild cytotoxic activity against human Hela and Daoy tumor cells.     

1H and 13C NMR assignments of eight nitrogen containing compounds from Nocardia alba sp.nov (YIM 30243T)

An unprecedented new natural product named nocarsin A (1), 5H‐4a,6,7a‐triazacyclopenta[cd]indene‐5,7(6H)‐dione (1), together with seven known compounds lumichrome (2), cyclo (L ‐Leu‐L ‐Tyr) (3), cyclo (L ‐Ala‐L ‐Ile) (4), cyclo (L ‐Ala‐L ‐Leu) (5), cyclo (L ‐Val‐L ‐Ala) (6), 5‐methyluracil (7) and uracil (8), was isolated from Nocardia alba sp.nov (YIM 30243^T), which was isolated from a soil sample collected from Yunnan Province, P. R. China. NMR techniques including COSY, HSQC, ROESY, and HMBC were used to elucidate the structures of these compounds. We report the unambiguous assignments of the ¹H and ¹³C NMR spectra of the new compound nocarsin A (1). Copyright © 2009 John Wiley & Sons, Ltd.     

A New Nortriterpene from the Root of Celastrus hypoleucus

A new nortriterpene, 2‐hydroxy‐3‐methyl‐21‐oxo‐12,24‐dinor‐D : B‐friedooleana‐1,3,5(10),7‐tetraen‐29‐oic acid ( 1 ), was isolated from the root of Celastrus hypoleucus, together with the two known compounds, celastorol ( 2 ) and pristimerine ( 3 ). Their structures were elucidated on the basis of spectroscopic analyses. Compounds 1 – 3 exhibited in vitro significant antioxidant (against lipid peroxidation; by the TBARS method) and antitumor activities (against cancer cell lines P‐388, A‐549, HL‐60, and BEL‐7402).     

New Eremophilane Sesquiterpenes from a Rhizome Extract of Petasites hybridus

A total of 21 natural products, 1 – 21 , were isolated from a supercritical CO₂ extract of the rhizomes of Petasites hybridus. Thereby, seven new eremophilane (= (1S,4aR,7R,8aR)‐decahydro‐1,8a‐dimethyl‐7‐(1‐methylethyl)naphthalene) sesquiterpenes, compounds 4, 5, 9, 11, 12, 15 , and 17 , were identified. The new constituent 9‐hydroxyisobakkenolide ( 15 ) is the first representative of a group of compounds closely related to the well‐known, but rare, bakkenolides. Tsoongianolide B ( 18 ) and its degradation product ligularenolide ( 19 ) were found as new Petasites constituents as well. The known eremophilanolide 2 was isolated from a plant source for the first time and the oxofuranopetasin 16 was isolated for the first time from the rhizomes of P. hybridus, together with eight other known compounds. The C(8)‐epimeric 2‐[(tigloyl)oxy]eremophilanolides 3 and 8 could clearly be differentiated. All structures were established by extensive 1D‐ and 2D‐NMR experiments (Tables 1–3), and confirmed by in‐depth GC/MS and HPLC/MS experiments.     

A New Diterpenoid and a New Diterpenoid Alkaloid from Aconitum coreanum

A new diterpenoid, guan fu diterpenoid A ( 1 ), and a new diterpenoid alkaloid, guan fu base S ( 2 ), were isolated from the Chinese medicinal herb Aconitum coreanum (Lèvl. ) Rapaics , together with five known diterpenoid alkaloids guan fu base P, guan fu base R, guan fu base G, guan fu base F, and guan fu base Z. The structures of the two new compounds were elucidated as ent‐kaurane‐16,20‐diol ( 1 ) and (11β,13S)‐2,3,15,16‐tetradehydro‐16,17‐dihydrohetisan‐11,13,14‐triol 11,13‐diacetate ( 2 ) on the basis of HR‐MS and 2D‐NMR analyses. This is the first report of an ent‐kaurane diterpenoid in Aconitum coreanum.     

Enantioselective Allylic Alkylation Catalyzed by Novel C2‐Symmetric Bisphosphinites

In this article, we present our results concerning new C₂‐symmetric bisphosphinites with a (1R,2R)‐1,2‐bis([1,1′: 3′,1″‐terphenyl]‐5′‐yl)ethane backbone. For the given chirality of the backbone, derivatives with aromatic and aliphatic substituents at the donor P‐atoms were synthesized with moderate yields in a straightforward manner. These compounds were evaluated in the Pd⁰‐catalyzed enantioselective allylic alkylations (up to 67% ee).     

Versatile and Efficient Synthesis of a New Class of Aza‐Based Phosphinic Amide Ligands via Unusual P?C Cleavage

A new class of bidentate, aza‐based phosphinic amide ligands of the type RN(H)P(?O)(2‐py)₂ (2‐py = 2‐pyridyl) was synthesized within minutes via a one‐pot process including Staudinger reaction of an organic azide (RN₃) with 2‐pyridylphosphines, followed by partial, unprecedented hydrolysis under loss of one aromatic substituent. The structure of the unusual‐hydrolysis product H₂C?CH(CH₂)₉N(H)P(?O)(2‐py)₂ ( 5a ) was characterized by IR, ¹H‐ and ³¹P‐NMR, as well as by X‐ray crystal‐structure analysis (Figure). The tetrahedral P‐atom was found to be surrounded by a trigonal‐pyramidal arrangement of the substituents. To gain insight into the formation of these novel phosphinic amides, a series of intermediate iminophosphoranes, H₂C?CH(CH₂)₉N?P(Ar)_n(2‐py)_{3 ? n} (n = 0–3), compounds 1a – 1f , were synthesized, and their hydrolyses were studied. All tested compounds followed the classical hydrolysis route of P?N cleavage under acidic conditions. Sequential hydrolysis to 5a – 5d only occurred under either basic conditions or in wet MeCN as solvent. Notably, H₂C?CH(CH₂)₉N?P(C₆H₅)(4‐MeO‐2‐py)₂ ( 1c ) was hydrolyzed at a much slower rate compared to its analogue 1b lacking the MeO group. On the contrary, the halogenated compounds H₂C?CH(CH₂)₉N?P(4‐X‐C₆H₄)₃ ( 1f,g ) (X = F, Cl) were hydrolyzed at a notably faster rate relative to the non‐halogenated congener 1e (X = H).     

‘Click Synthesis’ of Some Novel Benzimidazol Oxime Ethers Containing Heterocycle Residues as Potential ß‐Adrenergic Blocking Agents

The ‘click synthesis’ of some novel O‐substituted oximes, 5a – 5j , which contain heterocycle residues, as new analogs of ß‐adrenoceptor antagonists is described (Scheme 1). The synthesis of these compounds was achieved in four steps. The formation of (E)‐2‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylethanone oxime, followed by their reaction with 2‐(chloromethyl)oxirane, afforded mixture of oil compounds 3 and 4 , which by a subsequent tetra‐n‐butylammonium bromide (TBAB)‐catalyzed reaction with N H heterocycle compounds (Scheme 1), led to the target compounds 5a – 5j in good yields.     

Methyl Pothoscandensate,a New ent‐18(4→3)‐Abeokaurane from Pothos scandens

Methyl pothoscandensate ( 1 ), a new molecular skeleton of ent‐18(4→3)‐abeokaurane, along with eight known compounds was isolated from the whole plant of Pothos scandens. The structure of the new compound was established by spectroscopic techniques and confirmed by single‐crystal X‐ray diffraction. The inhibitory activity of selected compounds against porcine respiratory and reproductive syndrome virus (PRRSV) was measured by the cytopathic effect (CPE) method. Compound 1 showed weak effect on PRRSV with an IC₅₀ value of 40.3±8.3 μM (TI=15.7).     

Der erste viergliedrige Al/P‐Ring,der von drei Phosphoratomen und einem Aluminiumatom gebildet wird: Synthese und Kristallstruktur von [Cp*Al(PtBu)3]

The First Four‐Membered Al/P Ring formed by three Phosphorus Atoms nd one Aluminium Atom: Synthesis and Crystal Structure of [Cp*Al(P t Bu)₃] (AlCp*)₄ reacts with (PtBu)₃ at 90 °C to form the new cyclic Al/P‐compound 1,2,3‐tris‐t‐butyl‐tri‐phospha‐4‐pentamethylcyclopentadienylaluminetane: [Cp*Al(PtBu)₃] ( 1 ). 1 has been characterised by single crystal x‐ray diffraction, ³¹P{¹H}‐NMR spectroscopy as well as mass spectroscopy. It consists of a folded four‐membered AlP₃‐ring and differs therefore from all Al/P‐compounds known so far, which always show alternating Al‐P‐positions. 1 crystallises in the orthorhombic spacegroup P2₁2₁2₁, the lattice constants are: a = 9.067 pm, b = 16.212 pm, c = 17.449 pm, α = β = γ = 90°.     

Two New N‐(O‐Carbamoylglucopyranosyl)‐N‐dimethylansamitocins from Actinosynnema pretiosum

Two new and a known N‐(O‐carbamoylglucopyranosyl)ansamitocins were isolated from Actinosynnema pretiosum ssp. auranticum ATCC 31565. The known N‐(4‐O‐carbamoyl‐β‐D ‐glucopyranosyl)‐N‐demethylansamitocin P 2 (=ACGP‐2; 1 ) was assigned according to 1D‐ and 2D‐NMR data, and the two new compounds were identified as N‐(6‐O‐carbamoyl‐β‐D ‐glucopyranosyl)‐N‐demethylansamitocin P 2 (=ACGP‐2′; 2 ) and N‐(4‐O‐carbamoyl‐β‐D ‐glucopyranosyl)‐N‐demethylansamitocin P 1 (=ACGP‐1; 3 ) on the basis of spectroscopic data interpretation including 2D‐NMR and tandem MS analysis.