Facile Synthesis of 7‐epi‐Taxane and Its Derivatives and Preliminary Evaluation of Anticancer Activity

7‐epi‐Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7‐hydroxyl group simply using Ag₂O as catalyst and DMF as solvent. The catalyst could be quantitatively recovered by filtration without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives (e.g., docetaxel and paclitaxel) to 7‐epi‐taxane derivatives (e.g., 7‐epi‐docetaxel and 7‐epi‐paclitaxel). Furthermore, 33 ester derivatives of 7‐epi‐taxane with different amino acid moieties at the position of C‐13 were successfully synthesized via esterification without protecting C‐7‐OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with IC₅₀ value as low as 15.9 nmol/L for 18 .     

Taxane Diterpenoids from the Root Bark of Taiwanese Yew Taxus Mairei

Nineteen compounds including taxumairol R (1) , taxinine M (2) , taxacin (3) , paclitaxel (4) , 10‐deacetyltaxol A (5) , 10‐deacetyl‐7‐epi‐taxol (6) , 7‐epi‐taxol (7) , taxol C, 10‐deacetyltaxol C, 7β‐xylosyl‐10‐deacetyltaxol (8) , taxamairin A (9) , taxinine A, 14β‐hydroxytaxusin (10) , 5α‐hydroxy‐7β,9α,10β, 13α‐tetraacetoxy‐4(20), 11‐taxadiene, 1‐dehydroxybaccatin‐VI, 1β‐dehydroxybaccatin‐IV, baccatin IV, baccatin VI and ponasterone A have been isolated and identified from the root bark of Taxus mairei. Among them, compound 1 was a new taxoid and compounds 11 and 7β‐xylosyl‐10‐deacetyltaxol pentaacetate were new derivatives prepared from 14β‐hydroxytaxusin (10) and 8 , respectively. Their structures and assignment were established on the basis of 2D‐NMR analysis and chemical methods.     

Ferrocenyl,Alkyl, and Aryl‐Pyrido[2,3‐d]Pyrimidines as Vasorelaxant of Smooth Muscle of Rat Aorta via cAMP Conservation Through Phosphodiesterase Inhibition

New pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , and 21 have been synthesized. The vasorelaxant effect on smooth muscle isolated from rat aorta, via PDEs inhibition, of these compounds along with other pyrido[2,3‐d]pyrimidines 14 , 15 , 16 , 17 , 18 , 19 , 20 reported earlier by our group, has also been determined. These pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 were synthesized by the reaction of ferrocenyl‐ethynyl ketones ( 1 , 2 , 3 , 4 ) or α‐alkynyl ketones ( 5 , 6 , 7 , 8 , 9 , 10 ) with 6‐amino‐1,3‐dimethyluracil using [Ni(CN)₄]^?4 as an active catalytic species, formed in situ in a Ni(CN)₂/NaOH/H₂O/CO/KCN aqueous system. Evaluation of the vasorelaxant effect of compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 demonstrated that all compounds relax the tissue in a concentration‐dependent manner. The structural changes do not alter the effectiveness; however, there are differences related to potency expressed as EC₅₀. Compounds 12 (7‐ferrocenyl‐1,3‐dimethyl‐5‐(m‐tolyl)‐pyrido[2,3‐d]pyrimidine) and 13 (7‐ferrocenyl‐1,3‐dipropyl‐5‐(4‐metoxyphenyl)‐pyrido[2,3‐d]pyrimidine) were the most potent compounds, even more than rolipram, reference drug; the EC₅₀ was 0.41 ± 0.02 μM and 0.81 ± 0.11 μM for 12 and 13 , correspondingly. The EC₅₀ of compounds 15 (7‐ferrocenyl‐1,3‐dimethyl‐5‐phenyl‐pyrido[2,3‐d]pyrimidine), 14 (7‐ferrocenyl‐5‐(3,5‐dimethoxyphenyl)‐1,3‐dimethylpyrido[2,3‐d]pyrimidine), and 19 (5‐n‐butyl‐7‐ethyl‐1,3‐dimethylpyrido[2,3‐d]pyrimidine) was similar to EC₅₀ of rolipram. Compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 significantly induce concentration‐dependent vasorelaxation in endothelium‐intact aortic rings. In addition, the relaxation responses to each compound in either endothelium‐intact or endothelium denuded aortic rings were comparable, suggesting that removal of the functional endothelium has no significant influence on its intrinsic vasorelaxant activity. In vitro capability of conserving cyclic‐AMP or cyclic‐GMP (adenosine and guanosine 3′, 5′‐cyclic monophosphate) via PDE inhibition for compounds 12 , 13 , 14 , 15 and 19 was evaluated. Compounds 15 and 19 show the highest percent inhibition effect (94.83% and 83.98%, respectively) for the decomposition of c‐AMP. Docking studies showed that the compound 15 was selective for the inhibition of PDE‐4.     

Yb2+3—xPd12—3+xP7 (x = 0.40): Different Ytterbium Species in a Substituted Structural Motif of the Zr2Fe12P7 Type

The new compound Yb_2+3—xPd_12—3+xP₇ x = 0.40(4)) was synthesized by sintering of a mixture of elemental components at 1100 °C with subsequent annealing at 800 °C. The crystal structure of Yb_2+3—xPd_12—3+xP₇ was solved and refined from X‐ray single‐crystal diffraction data: space group P6¯, a = 10.0094(4)Å, c = 3.9543(2)Å, Z = 1; R(F) = 0.022 for 814 observed unique reflections and 38 refined parameters. The atomic arrangement reproduces a structure motif of the hexagonal Zr₂Fe₁₂P₇ type in which one of the transition metal positions is substituted predominantly by ytterbium (Yb : Pd = 0.86(1) : 0.14). The ytterbium atoms are embedded in the 3D polyanion formed by palladium and phosphorus atoms. Two different environments for ytterbium atoms are present in the structure. Magnetic susceptibility measurements and XAS spectroscopy at the Yb L_III edge show the presence of ytterbium in two electronic configurations, 4?¹³ and 4?¹⁴. The following model was derived. Ytterbium atoms in the 3k site are in the 4?¹³ state, the two remaining positions contain ytterbium in intermediate‐valence states, giving totally 79 % ytterbium in the 4?¹³ electronic configuration.     

Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part II

Coenzyme F430 pentamethyl ester 2 was partially hydrolyzed to a mixture of the five F430 tetramethyl esters 7 – 11 , which were separated by HPLC and identified by means of a full NMR characterization. The tetramethyl ester with a free COOH group at the side chain at C(3) of F430 was coupled to the N‐terminus of the peptidic spacer? ligand construct 12 selected and studied as described before. The UV/VIS and NMR spectra in CH₂Cl₂/3,3,3‐trifluoroethanol 6 : 1 show that the new derivative, the Ni^II(3³‐dehydroxy‐8³,12²,13³,18²‐tetra‐O‐methyl‐F430‐3³‐yl)‐L ‐prolyl‐L ‐prolyl‐N^π‐methyl‐L ‐histidine methyl ester ( 13 ), is an intramolecular, pentacoordinate, paramagnetic complex. In the same solvent system, the parent 3³,8³,12²,13³,18²‐penta‐O‐methyl‐F430 ( 2 ) is four coordinate and diamagnetic even in the presence of equimolar 1H‐imidazole. Protonation of the axially coordinating histidine residue of 13 gave the diamagnetic tetracoordinate base‐off form, which allowed us to establish the constitution of 13 by NMR.     

Formation and Structure of an Anionic Ruthenaborane Compound:[Et4N][(PPh3)2ClRuB12H12]

在研究RuCl2(PPh3)3 和 closo-B10H102- 在乙醇中的反应时,意外分离得到一个阴离子型的钌硼烷化合物[Et4N][(PPh3)2ClRuB12H12], 并且经过红外光谱和单晶X射线衍射分析确证. 在其结构中,闭式B12H122-配体与Ru(II)中心通过三个B-H-Ru三中心-二电子键结合. 分析原因应是在通过文献方法制备闭式B10H102-时的少量副产物闭式B12H122-在反应体系中与RuCl2(PPh3)3反应而生成了标题化合物. 根据硼烷簇合物的电子计数规则, 标题化合物也可以看成是含有2n (n为簇顶点数)个骨架电子的pileo型簇合物, 具有加帽(capped)的闭式多面体骨架构型. 这是第一个阴离子型的含有闭式B12H122- 的钌化合物.     

Supramolecular patterns in benzyladeninium p‐toluenesulfonate

In the title compound (systematic name: 6‐benzylamino‐7H‐purin‐3‐ium p‐toluenesulfonate), C₁₂H₁₂N₅⁺·C₇H₇O₃S⁻, the adenine moiety exists as the N³‐protonated N⁷—H tautomer. The dihedral angle between the adenine ring system and the phenyl ring is 82.76 (11)°. Two of the sulfonate O atoms form C—H...O and N—H...O hydrogen bonds with the H atoms on the N and C atoms in the 3‐ and 8‐positions, respectively, of the adenine moiety, leading to a zigzag chain. Two antiparallel zigzag chains are linked by the remaining sulfonate O atom through Hoogsteen‐site H atoms (i.e. those on the N atoms in the 6‐ and 7‐positions) of the adenine moiety, leading to a double chain. An annulus formed by a pair of inversion‐related anions and cations has been identified. An intramolecular toluenesulfonate–phenyl C—H...π interaction is also present.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Utility of the Pfitzinger Reaction in the Synthesis of Novel Quinoline Derivatives and Related Heterocycles

2‐(2‐Amino‐3,5‐dinitrophenyl)‐2‐oxoacetic acid ( 2 ) was obtained from hydrolysis of 5,7‐dinitroisatin ( 1 ) in alkaline media. A novel quinoxaline derivative ( 3 ) was synthesized from the reaction of the same compound ( 1 ) with o‐phenylenediamine. Reacting 2 with ethyl 3‐oxo‐3‐phenylpropanoate yields 6,8‐dinitro‐2‐phenylquinoline‐3,4‐dicarboxylic acid ( 4 ). Then, 4 was converted into new quinoline‐diacylchloride, quinoline‐ester, quinoline‐dicarboxamide, pyridazine, and pyrroledione derivatives ( 5 , 6a , 6b , 6c , 6d , 7a , 7b , 7c , 7d , 8 , 9 , 10a , 10b , 10c , 10d , 11a , 11b , 12 ) with SOCl₂, alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by ¹H NMR, ¹³C NMR, IR, mass and elemental analysis methods.     

Understanding the Biosynthesis of Paxisterol in Lichen-Derived Penicillium aurantiacobrunneum for Production of Fluorinated Derivatives

The U.S. endemic lichen (Niebla homalea)-derived Penicillium aurantiacobrunneum produced a cytotoxic paxisterol derivative named auransterol (2) and epi-citreoviridin (6). Feeding assay using ¹³C₁-labelled sodium acetate not only produced C-13-labelled paxisterol but also confirmed the biosynthetic origin of the compound. The fluorination of bioactive compounds is known to improve pharmacological and pharmacokinetic effects. Our attempt to incorporate the fluorine atom in paxisterol and its derivatives using the fluorinated precursor sodium monofluoroacetate resulted in the isolation of 7-monofluoroacetyl paxisterol (7). The performed culture experiment, as well as the isolation and structure elucidation of the new fluorinated paxisterol, is discussed herein.     

A Large Scale Separation of Taxanes from the Bark Extract of Taxus yunnanesis and 1H‐ and 13C‐NMR Assignments for 7‐epi‐10‐Deacetyltaxol

A large‐scale separation of paclitaxel from semi‐purified bark extract of Taxus yunnanesis was investigated. The chromatographic behavior of paclitaxel and two dose editing analogues, cephalomannine and 7‐epi‐10‐deacetyltaxol were systematically studied on a C₁₈ bonded phase column with different mobile phase in reverse phase mode. According to the notably different selectivity of the methanol and acetonitrile with water in the mobile phase and the most important requirement of capacity in preparative chromatography, the optimum suitably mobile phase used in a large‐scale isolation of paclitaxel and 7‐epi‐10‐deacetyltaxol on a preparative C₁₈ column was given. Cephalomannine was eliminated by ozonolysis and after then separated throughout a normal phase silica column. The whole large‐scale process for high purity paclitaxel from the bark extract of Taxus yunnanesis consisted of a preliminary purification with Biotage FLASH 150i system based on a prepacked normal phase silica cartridge followed by using a C₁₈ Nova‐pak? column in Waters PrepLC? 4000 preparative HPLC system. The structure of 7‐epi‐10‐deacetyltaxol was elucidated by 2D NMR technologies of TOCSY, DQF‐COSY, HMQC and HMBC, etc.     

Struktur und Eigenschaften von 5-epi-Flavoxanthin und 5-epi-Chrysanthemaxanthin

Structure and properties of 5-epi-flavoxanthin and 5-epi-chrysanthemaxanthin The absolute configurations of 5-epi-flavoxanthin ( 6 ) and 5-epi-chrysanthemaxanthin ( 7 ) prepared by acid catalysed rearrangement of semi-synthetic lutein epoxide 5 are shown to be (3S, 5S, 8R, 3′R, 6′R) and (3S, 5S, 8S, 3′R, 6′R), respectively. Contrary to published data [5] the relationship of the polyene chain and H₃(18) on the dihydrofurane ring is cis for the pair of stereoisomers having a Δδ = δ (H? C(7)) ? δ (H? C(8)) = 0,22 ppm and ³J ≡ 0. These conclusions are in full accord with the chiroptical data.     

Diselenastanna‐, ‐sila‐ and ‐carbacycles with an annelated dicarba‐closo‐dodecaborane(12) unit

The reactions of the 1,2‐diselenolato‐1,2‐dicarba‐closo‐dodecaborane(12) dianion 1 with diorganoelement(IV) dichlorides (Ph₂CCl₂, Me₂SiCl₂, Ph₂SiCl₂, Me₂SnCl₂, Ph₂SnCl₂) gave novel five‐member heterocycles along with other products. The molecular structures of the five‐member rings containing CPh₂ ( 2 ) and SnPh₂ ( 9 ) moieties between the selenium atoms were determined by X‐ray analyses. In the case of the chlorosilanes, the analogous five‐member ring containing the SiPh₂ unit ( 4 ) could be identified in mixtures. The expected reaction was accompanied by rearrangement leading to formation of another five‐member ring 6 containing the Ph₂Si? Se? Se moiety. Oxidative addition of the five‐member heterocycles containing tin ( 7, 9 ) to ethene‐bis(triphenylphosphane)platinum(0) gave at low temperature the bis(triphenylphosphane)platinum(II) complexes 12 and 13 , where the Pt(PPh₃)₂ fragment had been inserted into one of the Sn? Se bonds. Extensive decomposition of these complexes was observed above ? 20 °C. The proposed solution‐state structures of the new compounds are supported by multinuclear magnetic resonance data (¹H, ¹¹B, ¹³C, ²⁹Si, ³¹P, ⁷⁷Se, ¹¹⁹Sn and ¹⁹⁵Pt NMR). Copyright © 2007 John Wiley & Sons, Ltd.     

1,2‐, 1,7‐ and 1,12‐Dicarba‐closo‐dodecaborane(12) Derivatives Revisited by 13C NMR Spectroscopy and DFT Calculations. First Observation of Isotope‐Induced Chemical Shifts 1Δ10/11B(13C), and the Signs and Magnitudes of Coupling Constants 1J(13C,13C) and 1J(13C,11B)

The origin of broadening of ¹³C(carborane) NMR signals of 1,2‐, 1,7‐ and 1,12‐dicarba‐closo‐dodecaboranes(12) and several diphenylsilyl derivatives has been examined in detail and could be traced only partially to unresolved ¹³C–¹¹B spin‐spin coupling. Other contributions to the line widths arise from ¹³C–¹H dipole‐dipole interactions and, in particular, from isotope‐induced chemical shifts ¹Δ^10/11B(¹³C), observed here for carboranes for the first time. In the case of 1‐diphenylsilyl‐1,2‐dicarba‐closo‐dodecaborane(12), the coupling constant ¹J(¹³C,¹³C) = 9.3 Hz was measured in natural abundance of ¹³C. The small value of this coupling constant and its negative sign is predicted by calculations based on optimised structures [B3LYP/6‐311+G(d,p) level of theory] of the parent carboranes and 1‐silyl‐1,2‐dicarba‐closo‐dodecaborane(12) as a model compound [calcd. ¹J(¹³C,¹³C) = –10.5 Hz]. Calculated coupling constants ¹J(¹³C,¹¹B) are small (<7 Hz), in contrast to published assumptions, and of either sign, whereas ¹J(¹¹B,¹¹B) are all positive and range up to 15 Hz.     

Synthesis and Reactions of New Dithiolopyrroles

The title compounds were prepared starting from pyrrolinone 4 . Nucleophilic‐displacement and ring‐closure reactions yielded the dithiolopyrrole 5a , which formed salts with electrophiles ( 7, 8 ) as well as with bases. The crystal structure of 5a was determined. Oxidation of the dithioles 5a and 6a led to S(2)‐oxides ( 10a, 11a ) and the corresponding S(2)‐dioxides ( 10b, 11b ) depending on reaction conditions. The thiosulfinate 10a was converted by a ring‐opening/ring‐closure reaction sequence to the bicyclic sulfinamide 12 . The oxidative addition reactions of [Pt(η²‐C₂H₄) (PPh₃)₂] ( 14 ) with the disulfides 5a and 13 led to the dithiolatoplatinum(II) complexes 15 and 16 , respectively. Complex 16 was characterized structurally. The sulfenato‐thiolato complex 17 was synthesized via reaction of 14 with the thiosulfinate 10a . The thiosulfonato Pt^II complex 18 was prepared by an oxidative insertion of Pt⁰ into the C? S bond of the corresponding thiosulfonate 10b . Furthermore, complex 18 was characterized by single‐crystal X‐ray‐diffraction studies.     

The Total Synthesis and Biological Assessment of trans‐Epothilone A

The total synthesis of (12S,13S)‐trans‐epothilone A ( 1a ) was achieved based on two different convergent strategies. In a first‐generation approach, construction of the C(11) C(12) bond by Pd⁰‐catalyzed Negishi‐type coupling between the C(12)‐to‐C(15) trans‐vinyl iodide 5 and the C(7)‐to‐C(11) alkyl iodide 4 preceded the (nonselective) formation of the C(6) C(7) bond by aldol reaction between the C(7)‐to‐C(15) aldehyde 25 and the dianion derived from the C(1)‐to‐C(6) acid 3 . The lack of selectivity in the aldol step was addressed in a second‐generation approach, which involved construction of the C(6) C(7) bond in a highly diastereoselective fashion through reaction between the acetonide‐protected C(1)‐to‐C(6) diol 31 (‘Schinzer's ketone') and the C(7)‐to‐C(11) aldehyde 30 . As part of this strategy, the C(11) C(12) bond was established subsequent to the critical aldol step and was based on B‐alkyl Suzuki coupling between the C(1)‐to‐C(11) fragment 40 and C(12)‐to‐C(15) trans‐vinyl iodide 5 . Both approaches converged at the stage of the 3‐O, 7‐O‐bis‐TBS‐protected seco acid 27 , which was converted to trans‐deoxyepothilone A ( 2 ) via Yamaguchi macrolactonization and subsequent deprotection. Stereoselective epoxidation of the trans C(12) C(13) bond could be achieved by epoxidation with Oxone ^® in the presence of the catalyst 1,2 : 4,5‐di‐O‐isopropylidene‐L ‐erythro‐2,3‐hexodiuro‐2,6‐pyranose ( 42a ), which provided a 8 : 1 mixture of 1a and its (12R,13R)‐epoxide isomer 1b in 27% yield (54% based on recovered starting material). The absolute configuration of 1a was established by X‐ray crystallography. Compound 1a is at least equipotent with natural epothilone A in its ability to induce tubulin polymerization and to inhibit the growth of human cancer cell lines in vitro. In contrast, the biological activity of 1b is at least two orders of magnitude lower than that of epothilone A or 1a .     

Synthesis and Supramolecular Assemblies of Tripodal 1,3,5‐Tris(phenoxymethyl)‐2,4,6‐triethylbenzene Analogues

Tripodal 1,3,5‐tris(phenoxymethyl)‐2,4,6‐triethylbenzene analogues have been synthesized and structurally characterized by IR, ¹H NMR and ¹³C NMR spectroscopy and HRMS, and additionally, the single crystal structures of compounds bearing ortho‐ ( 7 ), meta‐ ( 9 ) and para‐hydroxymethyl ( 11 ) functions have been determined by X‐ray diffraction analysis. The structural study revealed that compounds 7 , 9 , and 11 do not adopt the expected 1,3,5‐alternate conformation in the solid state. The packing diagrams of compounds 7 , 9 , and 11 revealed that six hydrophilic hydroxymethyl groups from six individual molecules ( 7 , 9 and 11 ) were arranged in close contact via intermolecular hydrogen‐bond interactions. For compounds 7 and 9 , the six hydroxyl groups formed a distorted hexagonal ring; however, formation of such a hexagonal ring was not clear in the case of compound 11 . Compounds 9 and 11 were found to form hydrophobic cavities via intermolecular hydrogen‐bond interactions in the solid state, and the cavities were occupied by two ethyl groups from the two cavity‐forming molecules.     

Structural Revision and Elucidation of the Biosynthesis of Hypodoratoxide by 13C,13C COSY NMR Spectroscopy

Feeding of (2,3,4,5,6‐¹³C₅)mevalonolactone to the fungus Hypomyces odoratus resulted in a completely labeled sesquiterpene ether. The connectivity of the carbon atoms was easily deduced from a ¹³C,¹³C COSY spectrum, revealing a structure that was different from the previously reported structure of hypodoratoxide, even though the reported ¹³C NMR data matched. A structural revision of hypodoratoxide is thus presented. Its absolute configuration was tentatively assigned from its co‐metabolite cis‐dihydroagarofuran. Its biosynthesis was investigated by feeding of (3‐¹³C)‐ and (4,6‐¹³C₂)mevalonolactone, which gave insights into the complex rearrangement of the carbon skeleton during terpene cyclization by analysis of the ¹³C,¹³C couplings.     

Three New Cadinene Derivatives from Xenia Puerto‐Galerae

Chromatographic investigation of an acetone extract of the octocoral Xenia puerto‐galerae afforded three new cadinene sesquiterpenes; 8‐epi‐xenitorin A ( 1 ), 10‐epi‐xenitorin C ( 2 ), and 7‐isopropenyl‐4,10‐dimethyl‐2,3,4,5‐tetrahydronaphthalene ( 3 ), in addition to four known cadinene analogs ( 4 , 11–13 ) and six xenicanes ( 5–10 ). The structures were elucidated through spectroscopic analysis, especially 2D NMR. A biogenetic pathway of 1–3 and analogs was proposed.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.