Sterols from the Stems of Momordica charantia

A new sterol, 5α,6α‐epoxy‐3β‐hydroxy‐(22E,24R)‐ergosta‐8,22‐dien‐7‐one ( 1 ), together with eight known sterols, 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7α‐diol ( 2 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7β‐diol ( 3 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8(14),22‐diene‐3β,7α‐diol ( 4 ), 3β‐hydroxy‐(22E,24R)‐ergosta‐5,8,22‐trien‐7‐one ( 5 ), ergosterol peroxide ( 6 ), clerosterol ( 7 ), decortinol ( 8 ), and decortinone ( 9 ), were isolated from the stems of Momordica charantia. Their structures were elucidated by mean of extensive spectroscopic methods, including ¹H, ¹³C, 2D‐NMR and HR‐EI‐MS, as well as comparison with the literature data. Compounds 1 , 4 , 5 , 8 , and 91 were not cytotoxic against the SK‐Hep 1 cell line.     

Cytotoxic Activity of Capnellene‐8β, 10α‐Diol Derivatives from a Taiwanese Soft Coral Capnella sp.

The sesquiterpene capnellene‐8β, 10α‐diol ( 1 ) was isolated from non‐polar extract of the soft coral Capnella sp. Ten acylation products of capnellene‐8β, 10α‐diol were prepared: 10α‐hydroxy‐8β‐O‐benzoylcapnellene ( 2 ), 10α‐hydroxy‐8β‐O‐p‐toluoylcapnellene ( 3 ), 10α‐hydroxy‐8β‐O‐4‐chlorobenzoyl‐capnellene ( 4 ), 10α‐hydroxy‐8β‐O‐2‐furoylcapnellene ( 5 ), 10α‐hydroxy‐8β‐O‐2‐thiophenoylcapnellene ( 6 ), 10α‐hydroxy‐8β‐O‐4‐fluorobenzoylcapnellene ( 7 ), 10α‐hydroxy‐8β‐O‐4‐propylbenzoylcapnellene ( 8 ), 10α‐hydroxy‐8β‐O‐cinnamoylcapnellene ( 9 ), 10α‐hydroxy‐8β‐O‐4‐nitrobenzoylcapnellene ( 10 ), and 10α‐hydroxy‐8β‐O‐4‐anisoylcapnellene ( 11 ). The structures of capnellene‐8β, 10α‐diol as well as its derivatives were established through standard spectroscopic analysis. The in vitro cytotoxic activities of the eleven compounds were evaluated against Hela, KB, Daoy, and WiDr human tumor cell lines.     

1H and 13C NMR signal assignments of carboxyl‐linked glucosides of bile acids

Complete ¹H and ¹³C resonance assignments were carried out for a new type of carboxyl‐linked glucosides of chenodeoxycholic (3α,7α‐dihydroxy‐5β‐cholan‐24‐oic) and hyodeoxycholic (3α,6α‐dihydroxy‐5β‐cholan‐24‐oic) acids by using several homonuclear (¹H–¹H) and heteronuclear (¹H–¹³C) 2D NMR techniques. Differences in the ¹H and ¹³C resonances between the α‐ and β‐anomers of the ester glucosides of bile acids were clarified for the first time. A comparison of the ¹H and ¹³C signal shifts induced by β‐D ‐glucosidation at the 24‐carboxyl and 3α‐hydroxyl groups in the parent 5β‐cholanoic acid was also made. Copyright © 2003 John Wiley & Sons, Ltd.     

Lycopodium Alkaloids from Huperzia serrata

Three new lycopodium alkaloids, huperserramines A–C ( 1 – 3 , resp.), along with 15 known ones, lycopodine‐6α,11α‐diol ( 4 ), lycoposerramine H ( 5 ), lycoposerramine I ( 6 ), lycopodine‐6α‐ol ( 7 ), lycoposerramine M ( 8 ), diphaladine A ( 9 ), lycoposerramine K ( 10 ), lycoposerramine W ( 11 ), huperzine M ( 12 ), luciduline ( 13 ), phlegmariuine N ( 14 ), huperzine A ( 15 ), huperzine B ( 16 ), lycodine ( 17 ), and lycoposerramine R ( 18 ), were isolated from the whole plant of Huperzia serrata. Their structures were established by spectroscopic methods, including 2D‐NMR and MS analyses. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α‐glucosidase. As a result, lycopodine‐6α,11α‐diol ( 4 ) exhibited more potent α‐glucosidase inhibitory activity (IC₅₀ 148±5.5 μM ) than the positive control acarbose (IC₅₀ 376.3±2.7 μM ).     

Theoretical Study Of β2,3‐Peptide Models

Conformational features of α,β‐disubstituted β^2,3‐dipeptide models have been studied with quantum mechanics method. Geometries were optimized with the HF/6‐31G** method, and energies were evaluated with the B3LYP/6‐31G** method. Solvent effect was evaluated with the SCIPCM method. For (2S,3S)‐β^2,3‐dipeptide model 1 , a six‐membered‐ring hydrogen bonded structure is most stable. However, the conformation corresponding to the formation of the 14‐helix is only about 1.7 kcal/mol less stable in methanol solution, indicating that the 14‐helix is favored if a (2S,3S)‐β^2,3‐polypeptide contains more than 5 residues. On the other hand, the conformation corresponding to the formation of β‐sheet is most stable for (2R,3S)‐β^2,3‐dipeptide model 2 , suggesting that this type of β‐peptides is intrinsically favored for the formation of β‐sheet secondary structure.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.     

Semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane diterpene

Annonalide (3β,20‐epoxy‐3α,16‐dihydroxy‐15‐oxo‐7‐pimaren‐19,6β‐olide, C₂₀H₂₆O₆, 1 ) is the major (9βH)‐pimarane diterpene isolated from tubers of Cassimirella ampla, and it exhibits cytotoxic properties upon interaction with ctDNA. We have prepared new derivatives of 1 by modification of the (9βH)‐pimarane backbone and report here the semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane. Our approach was the reduction of the carbonyl groups of 1 with sodium borohydride, at positions C15 (no stereoselectivity) and C3 (stereoselective reduction), followed by rearrangement of the 6,19‐γ‐lactone ring into the six‐membered 19,20‐δ‐lactone ring in 4a (3β,6β,16‐trihydroxy‐7‐pimaren‐19,20β‐olide monohydrate, C₂₀H₃₀O₆·H₂O). The absolute structure of the new compound, 4a , was determined unambiguously with a Flack parameter x of −0.01 (11), supporting the stereochemistry assignment of 1 redetermined here. Besides the changes in the pattern of covalent bonds caused by reduction and lactone rearrangement, the conformation of one of the three fused cyclohexane rings is profoundly different in 4a , adopting a chair conformation instead of the boat shape found in 1 . Furthermore, the intramolecular hydrogen bond present in 1 is lost in new compound 4a , due to hydrogen bonding between the 3‐OH group and the solvent water molecule.     

Two isomers of 2,4‐di­benzyl‐8‐azabicyclo­[3.2.1]­octan‐3‐ol

The crystal structures of the title compounds, 2α,4α‐di­benzyl‐3α‐tropanol (2α,4α‐di­benzyl‐8‐methyl‐8‐aza­bi­cyclo­[3.2.1]­octan‐3α‐ol), C₂₂H₂₇NO, (I), and 2α,4α‐di­benzyl‐3β‐tropanol (2α,4α‐di­benzyl‐8‐methyl‐8‐aza­bi­cyclo­[3.2.1]­octan‐3β‐ol), C₂₂H₂₇NO, (II), show that both compounds have a piperidine ring in a chair conformation and a pyrrolidine ring in an envelope conformation. Isomer (I) is asymmetric, the benzyl groups having different orientations, whereas isomer (II) is mirror symmetric, and the N and O atoms, the C atom attached to the hydroxy group, and the methyl C atom attached to the N atom lie on the mirror plane. In the crystal structures of both (I) and (II), the mol­ecules are linked together by intermolecular O—H⋯N hydrogen bonds to form chains that run parallel to the a direction in (I) and parallel to b in (II).     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

Theoretical study of structural features of endo,exo double bonds and side chain in 14α‐demethylation of lanosterol

The 14α‐demethylation of biosynthetic reactions is carried out exclusively by lanosta‐8,24‐dien‐3β‐ol (lanosterol). Theoretical calculations were done to determine the importance of this structure with the Hartree–Fock scheme. It was modeled on structures similar to lanosterol with variations on the endo between C8? C9 (lanosta‐7,24‐dien‐3β‐ol and lanosta‐6,24‐dien‐3β‐ol) as compared with the exo between C24? C25 (Lanosta‐8‐en‐3β‐ol) and the size of the side chain (27‐norlanosta‐8‐en‐3β‐ol, 26,27‐dinorlanosta‐8‐en‐3β‐ol, 25,26,27‐trinorlanosta‐8‐en‐3β‐ol, 24,25,26,27‐tetranorlanosta‐8‐en‐3β‐ol, 23,24,25,26,27‐pentanorlanosta‐8‐en‐3β‐ol, 22,23,24,25,26,27‐hexanorlanosta‐8‐en‐3β‐ol). Energetic, electronic, and orbital evidence was found. The theoretical data were analyzed and were found to be important for the 14α‐demethylation, the presence of HOMO on the region C8? C9 and C14? C14¹, a negative charge on the outgoing methyl C14¹. This atomic charge varies with the size of the side chain, and with the modification of the endo and exo double bonds. The conformation of the structure of the steroid is also related to its reactivity. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

16α,17α‐Epoxy‐20‐oxopregn‐5‐en‐3β‐yl acetate

The title compound, C₂₃H₃₂O₄, has a 3β configuration, with the epoxy O atom at 16α,17α. Rings A and C have slightly distorted chair conformations. Because of the presence of the C5=C6 double bond, ring B assumes an 8β,9α‐half‐chair conformation slightly distorted towards an 8β‐sofa. Ring D has a conformation close to a 14α‐envelope. The acetoxy and acetyl substituents are twisted with respect to the average molecular plane of the steroid. The conformation of the mol­ecule is compared with that given by a quantum chemistry calculation using the RHF–AM1 (RHF = Roothaan Hartree–Fock) Hamiltonian model. Cohesion of the crystal can be attributed to van der Waals interactions and weak intermolecular C—H?O interactions, which link the mol­ecules head‐to‐tail along [101].     

Sterols from the Fungus Catathelasma imperiale

Eight ergostane-type sterols and three their derivatives (one mono-linoleate and two mono-glucosides) were isolated from the ethyl acetate soluble fraction of the fungus Catathelasma imperi.a/e. Two of them are novel compounds, namely 22E,24R-er-gosta-7,22-diene-3β ,5α-diol-6β-linoleate (1) and 22E, 24R-er-gosta-7,22-diene-3β, 5β, 6α-triol (5) with an uncommon c/s-fused A/B ring. Structures of these compounds were demon-strated on the basis of their chemical evidences and spectroscop-ic methods, especially 2D NMR techniques.     

Synthesis and Crystal Structures of O‐2′,3′‐Cyclic Cyclopentanone and Cyclohexanone Ketals of the Cytostatic 5‐Fluorouridine

The synthesis of two O‐2′,3′‐cyclic ketals, i.e., 5 and 6 , of the cytostatic 5‐fluorouridine ( 2 ), carrying a cyclopentane and/or a cyclohexane ring, respectively, is described. The novel compounds were characterized by ¹H‐, ¹⁹F‐, and ¹³C‐NMR, and UV spectroscopy, as well as by elemental analyses. Their crystal structures were determined by X‐ray analysis. Both compounds 5 and 6 show an anti‐conformation at the N‐glycosidic bond which is biased from +ac to +ap compared to the parent nucleoside 2 . The sugar puckering is changed from ^2′E to _3′E going along with a reduction of the puckering amplitude τ_m by ca. 10–13° due to the ketalization. The conformation about the sugar exocyclic bond C(4′)? C(5′) of 5 and 6 remains unchanged, i.e., g⁺, compared with compound 2 .     

An LC/MS method for the quantitative determination of 7α‐OH DHEA and 7β‐OH DHEA: an application for the study of the metabolism of DHEA in rat brain

Dehydroepiandrosterone (DHEA) is an important neurosteroid with neuronal protection and memory enhancement functions. 7α‐OH DHEA and 7β‐OH DHEA are the two important metabolites of DHEA in the brain. We have developed an LC/MS method to quantitatively analyze 7α‐OH DHEA and 7β‐OH DHEA. Chromatographic separation was carried out on a C₁₈ column with gradient elution using mobile phases of formic acid in acetonitrile and in water formic acid. Mass spectral detection was performed with a ThermoFinnigan LCQ advantage quadruple ion trap mass spectrometer with electrospray ionization. Positive ion chromatograms were acquired using single ion monitoring. The protonated molecule was 305 m/z, but the most abundant ion (269 m/z) was used for quantification. This method was validated and applied to investigate the 7‐hydroxylation of DHEA. When incubating DHEA with rat brain microsomes, both 7α‐OH DHEA and 7β‐OH DHEA were observed, but 7α‐OH DHEA was the major metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Cytotoxic Naphtho‐γ‐pyrones from the Mangrove Endophytic Fungus Aspergillus tubingensis (GX1‐5E)

Four new dimeric naphtho‐γ‐pyrones, named rubasperone D ( 1 ), rubasperone E ( 2 ), rubasperone F ( 3 ), and its atropisomer rubasperone G ( 4 ), together with four known monomeric naphtho‐γ‐pyrones, TMC 256 A1 ( 5 ), rubrofusarin B ( 6 ), fonsecin ( 7 ), and flavasperone ( 8 ), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1‐5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D‐ and 2D‐NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF‐7, MDA‐MB‐435, Hep3B, Huh7, SNB19, and U87 MG with IC₅₀ values between 19.92 and 47.98 μM . Compounds 1, 6 , and 8 also showed mild cytotoxic activity.     

The dangerous new synthetic drug α‐PVP as the hydrated chloride salt α‐pyrrolidinopentiophenone hydrochloride 0.786‐hydrate

α‐Pyrrolidinovalerophenone (α‐PVP), a dangerous designer drug, is now being marketed around the world as a harmless `bath salt', when in reality it is a powerful β‐ketone phenethylamine stimulant. A sample of the free base from a recent law‐enforcement seizure was crystallized as the HCl salt [systematic name: 1‐(1‐oxo‐1‐phenylpentan‐2‐yl)pyrrolidin‐1‐ium chloride 0.786‐hydrate], C₁₅H₂₂NO⁺·Cl⁻·0.786H₂O. In the crystal structure, the propyl chain is nearly perpendicular to both the phenyl ring and the carbonyl group. The hydrogen‐bonding scheme involves the quaternary N atom, the Cl⁻ anion and the partially occupied (0.786) water molecule, forming centrosymmetric dimers.     

Xanthone O‐Glycosides from the Roots of Pteris Multifida

Two new xanthone glycosides and six known compounds were isolated from the roots of Pteris multifida. Based on spectroscopic and chemical methods, the structures of the new compounds were elucidated as 1‐hydroxy‐4,7‐dimethoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 1 ), and 1,3‐dihydroxy‐7‐methoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1 →2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 2 ), respectively.     

Palladium‐catalyzed cyclization of β‐bromo‐α,β‐unsaturated ketones with arylhydrazines leading to 3‐substituted 1‐aryl‐1 H‐pyrazoles

β‐Bromo‐α,β‐unsaturated ketones are condensed with arylhydrazines to form hydrazones, which are in situ intramolecularly cyclized into 3‐substituted 1‐aryl‐1 H‐pyrazoles under a catalytic system of Pd(OAc)₂/1,3‐bis(diphenylhosphino)propane (dppp)/NaO^tBu. Copyright © 2012 John Wiley & Sons, Ltd.     

胆甾-4α-甲基-8-烯-3β，7α-二醇二乙酸酯的结构与性质研究

Lophenol, cholest-4α-methyl-7-en-3β-ol (1), obtained from Dracaena cochinchinensis (Lour.) S. C. Chen, was structurally modified. It was acetylated to protect 3β-hydroxyl group, and then oxidised by selenium dioxide in acetic acid to give cholest-4a-methyl-8-en-3β, Ta-diol diacetate (3). This compound 3 is unstable in chloroform solution or when heated and easily converted to a diene compound, cholest-4a-methyl-7,14-dien-3β-ol acetate (4). The structures of 3 and 4 were elucidated by means of IR, ^1H NMR, ^13C NMR and MS, and the absolute configuration of 3 was established by X-ray crystallography. The property of 3 was also discussed in this paper. Both 3 and 4 are new compounds and were reported for the first time.     

Triterpenoide. XIX. 3β‐Hydroxy‐11‐oxo‐18α‐olean‐12‐en‐28‐säure‐methyl­ester und 3,11‐Dioxo‐18α‐olean‐12‐en‐28‐säure‐methyl­ester

The X‐ray crystal structure analyses of 3β‐hydroxy‐11‐oxo‐18α‐olean‐12‐en‐28‐oic acid methyl ester ethanol solvate, C₃₁H₄₈O₄·C₂H₆O, (I), and 3,11‐dioxo‐18α‐olean‐12‐en‐28‐oic acid methyl ester, C₃₁H₄₆O₄, (II), are described. These two compounds differ only in the structure of ring A. In (I), ring A has a chair conformation, while in (II), it has a twisted boat conformation. In both compounds, ring C has a slightly distorted sofa conformation, rings B, D and E are in chair conformations, and rings D and E are trans‐fused. The asymmetric unit of (I) contains one mol­ecule of ethanol linked by hydrogen bonds with two different mol­ecules of (I).