Enantiospecific total synthesis of (-)-(E)16-epiaffinisine, (+)-(E)16-epinormacusine B,and (+)-dehydro-16-epiaffinisine as well as the stereocontrolled total synthesis of alkaloid G

An efficient strategy is described for the total synthesis of the sarpagine-related indole alkaloids (-)-(E)16-epiaffinisine (1), (+)-(E)16-epinormacusine B (2), and (+)-dehydro-16-epiaffinisine (4). A key step employed the chemospecific and regiospecific hydroboration/oxidation at C(16)-C(17); this method has also resulted in the synthesis of (+)-dehydro-16-epinormacusine B (5). The oxy-anion Cope rearrangement followed by protonation of the enolate that resulted under conditions of kinetic control has been employed to generate the key asymmetric centers at C(15), C(16), and C(20) in alkaloid G (7) in a highly stereocontrolled fashion (>43:1). Conditions that favor control of the sarpagine stereochemistry at C(16) vs the epimeric ajmaline configuration at the same stereocenter have been determined. The formation of the required cyclic ether in 4, 5, and 7 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF or DDQ/aq THF in excellent yields.     

Total synthesis of (-)-heptemerone B and (-)-guanacastepene E

A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the neodolastane diterpenoid heptemerone B has been completed. Saponification of (-)-heptemerone afforded (-)-guanacastepene E. The absolute stereochemistry of (-)-heptemerone B was thus established as 5-(S), the same as (-)-guanacastepene E. The longest linear sequence of the synthesis comprises 17 (18) steps from simple known starting materials. Our general synthetic approach integrates a diverse set of reactions, including an intramolecular Heck reaction to create one quaternary stereocenter and a cuprate conjugate addition for the establishment of the other. The central seven-membered ring was closed with an uncommon electrochemical oxidation, whereas the five-membered ring was formed through ring-closing metathesis. The absolute configuration of the two key building blocks was established through an asymmetric reduction and an asymmetric ene reaction.     

A facile and highly stereoselective synthesis of (2E)-, (2E,4E)-unsaturated amides and related natural products

A facile synthesis of (2E)-, (2E, 4E)-unsaturated amides was achieved via arsonium bromides with high stereoselectivity. Its application to the synthesis of related natural products 4 and 5 is also reported.     

Synthesis and Crystal Structure of（2E,6E）-2,6-bis（2,3-dimethoxybenzylidene）cyclohexanone

The new title compound (2E,6E)-2,6-bis(2,3-dimethoxybenzylidene)cyclohexanone (C 24 H 26 O 5,M r=394.45) has been synthesized,and its crystal structure was studied.The title compound crystallizes in the orthorhombic system,space group Pca2 1 with a=17.536(2),b=14.8515(16),c=8.0512(9),V=2096.8(4) 3,Z=4,D c=1.250 g/cm 3,λ=0.71073,μ=0.087 mm-1 and F(000)=840.The structure was solved by direct methods and refined to R=0.0533 and wR=0.1248 from 2727 observed reflections (I > 2σ(Ⅰ)).The title molecules are connected through hydrogen bonds to generate a 3-D supramolecule.The preliminary biological tests showed definitely biological activity for the title compound.     

Biomimetic total synthesis of litseaverticillols B, E, I, and J and structural reassignment of litseaverticillol E

[reaction: see text] The first total synthesis of litseaverticillols B (1), E (2), I (4), and J (5) as well as the structural reassignment of litseaverticillol E (2) have been achieved by means of a biomimetic sequence of transformations during which a [4 + 2]-initiated reaction cascade and an ene reaction, both involving singlet oxygen ((1)O(2)), formed key steps. The reassignment of the structure of litseaverticillol E (3) to include an allylic hydroperoxide provides strong support for our biogenetic hypothesis.     

Interaction of E6 Gene from Human Papilloma Virus 16 (HPV-16) with CdS Quantum Dots

The aim of this study was to analyze the interactions of blue and yellow fluorescent CdS quantum dots (CdS-QDs) with human papillomavirus 16 (HPV-16) oncogene E6. The interactions were investigated using chip capillary electrophoresis, spectrophotometry and square wave voltammetry (SWV). Using chip capillary electrophoresis we proved that blue fluorescent CdS-QDs (0.5 mM) caused an increase of the migration time of the E6 HPV-16 DNA–CdS-QDs complex by 42 s compared to control DNA (E6 HPV-16). The same concentration of yellow fluorescent CdS-QDs caused an increase in the migration time of the DNA–CdS-QDs complex by 108 s compared to the control DNA (E6 HPV-16). The difference in the migration times between both complexes was 66 s. Using square wave voltammetry (SWV), the reduction signal of cytosine and adenine (peak CA) was observed, after the complex with 2.5 µg mL^?1 DNA was formed. A decrease of the peak CA reduction signal of the complex DNA–CdS-QDs by 90 % was caused when yellow fluorescent CdS-QDs (0.03 mM) were used. The same concentration of blue fluorescent CdS-QDs caused only a 50 % decrease of the C and A reduction signal of the DNA–CdS-QDs complex. The difference between both CdS-QDs was 40 %. Electrochemical measurements and chip electrophoresis analyses confirmed that the yellow fluorescent CdS-QDs show higher affinity to the DNA (E6 HPV-16) compared to blue ones.     

Interaction of E6 Gene from Human Papilloma Virus 16 (HPV-16) with CdS Quantum Dots

The aim of this study was to analyze the interactions of blue and yellow fluorescent CdS quantum dots (CdS-QDs) with human papillomavirus 16 (HPV-16) oncogene E6. The interactions were investigated using chip capillary electrophoresis, spectrophotometry and square wave voltammetry (SWV). Using chip capillary electrophoresis we proved that blue fluorescent CdS-QDs (0.5 mM) caused an increase of the migration time of the E6 HPV-16 DNA–CdS-QDs complex by 42 s compared to control DNA (E6 HPV-16). The same concentration of yellow fluorescent CdS-QDs caused an increase in the migration time of the DNA–CdS-QDs complex by 108 s compared to the control DNA (E6 HPV-16). The difference in the migration times between both complexes was 66 s. Using square wave voltammetry (SWV), the reduction signal of cytosine and adenine (peak CA) was observed, after the complex with 2.5 µg mL⁻¹ DNA was formed. A decrease of the peak CA reduction signal of the complex DNA–CdS-QDs by 90 % was caused when yellow fluorescent CdS-QDs (0.03 mM) were used. The same concentration of blue fluorescent CdS-QDs caused only a 50 % decrease of the C and A reduction signal of the DNA–CdS-QDs complex. The difference between both CdS-QDs was 40 %. Electrochemical measurements and chip electrophoresis analyses confirmed that the yellow fluorescent CdS-QDs show higher affinity to the DNA (E6 HPV-16) compared to blue ones.

     

Concise syntheses of coronarin A, coronarin E, austrochaparol and pacovatinin A

Total syntheses of (+)-coronarin A (1), (+)-coronarin E (2), (+)-austrochaparol (3) and (+)-pacovatinin A (4) were achieved from the synthetic (+)-albicanyl acetate (6). Dess-Martin oxidation of (+)-albicanol (5) derived from the chemoenzymatic product (6) gave an aldehyde (7), which was subjected to Julia one-pot olefination using beta-furylmethyl-heteroaromatic sulfones (8 or 9 ) gave (+)-trans coronarin E (2) and (+)-cis coronarin E (12) with high cis-selectivity. The synthesis of (+)-coronarin A (1) from (+)-trans coronarin E (2) was achiev-ed, while (+)-cis coronarin E (12) was converted to the natural products (+)-(5S,9S,10S)-15,16-epoxy-8(17),13(16),14-labdatriene (13) and (+)-austrochaparol (3). By the asymmetric synthesis of (+)-3, the absolute structure of (+)-3 was determined to be 5S, 7R, 9R, 10S configurations. Homologation of (+)-albicanol (5) followed by allylic oxidation gave (7 alpha)-hydroxy nitrile (17), which was finally converted to the natural (+)-pacovatinin A (4) in 8 steps from (+)-albicanol (5).     

A theoretical and experimental study on the Lewis acid-base adducts (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) and (P(4)Se(3)).(NbCl(5))

The Lewis acid-base adducts (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) and (P(4)Se(3)).(NbCl(5)) have been prepared and characterized by Raman, IR, and solid-state (31)P MAS NMR spectroscopy. Hybrid density functional calculations (B3LYP) have been carried out for both the apical and the basal (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) adducts. The thermodynamics of all considered species has been discussed. In accordance with solid-state (31)P MAS NMR and vibrational data, the X-ray powder diffraction structures of (P(4)S(3)).(BBr(3)) [monoclinic, space group P2(1)/m (No. 11), a = 8.8854(1) A, b = 10.6164(2) A, c = 6.3682(1) A, beta = 108.912(1) degrees, V = 568.29(2) A(3), Z = 2] and (P(4)S(3)).(BI(3)) [orthorhombic, space group Pnma (No. 62), a = 12.5039(5) A, b = 11.3388(5) A, c = 8.9298(4) A, V = 1266.09(9) A(3), Z = 4] indicate the formation of an apical P(4)S(3) complex in the reaction of P(4)S(3) with BX(3) (X = Br, I). Basal adducts are formed when P(4)Se(3) is used as the donor species. Vibrational assignment for the normal modes of these adducts has been made on the basis of comparison between theoretically obtained and experimentally observed vibrational data.     

Total synthesis and absolute configuration of liverwort diterpenes, (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-Epoxy-18-hydroxysphenoloba-13(15),16-diene,by use of the ring closing metathesis reaction applied to seven-membered carbocycles with a trisubstituted double bond

Seven-membered cyclic compounds possessing trisubstituted double bonds have been effectively constructed employing the Grubbs catalyst to effect olefin metathesis. The keto ester does not undergo cyclization; however, alcohols protected by the silyl groups smoothly cyclized into seven-membered compounds. The product was successfully converted to (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene, liverwort diterpenes isolated from Anastrophyllum auritum to establish the absolute configuration.     

Synthesis and structure of heterometallic complexes (RhFe, CoFe) containing bridging 1,2-dicarba-closo-dodecarborane-1,2-dichalcogenolato ligands

The prototype hetero-binuclear complexes containing metal-metal bonds, {CpRh[E2C2(B10H10)]}[Fe(CO)3] (Cp = Cp* = eta 5-Me5C5, E = S(5a), Se(5b); Cp = Cp = eta 5-1,3-tBu2C5H3, E = S(6a), Se(6b)) and {CpCo[E2C2(B10H10)]}[Fe(CO)3] (Cp = Cp* = eta 5-Me5C5, E = S(7a), Se(7b); Cp = Cp = eta 5-C5H5, E = S(8a), Se(8b)) were obtained from the reactions of 16-electron complexes CpRh[E2C2(B10H10)] (Cp = Cp*, E = S(1a), Se(1b); Cp = Cp, E = S(2a), Se(2b)), CpCo[E2C2(B10H10)] (Cp = Cp*, E = S(3a), Se(3b); Cp = Cp, E = S(4a), Se(4b)) with Fe(CO)5 in the presence of Me3NO. The molecular structures of {Cp*Rh[E2C2(B10H10)]}[Fe(CO)3] (E = S(5a), Se(5b)), {CpRh[S2C2(B10H10)]}[Fe(CO)3] (6a) {Cp*Co[S2C2(B10H10)]}[Fe(CO)3] (7a) and {CpCo[S2C2(B10H10)]}[Fe(CO)3] (8a) have been determined by X-ray crystallography. All these complexes were characterized by elemental analysis and IR and NMR spectra.     

A mild conversion of phenylpropropnoid into rare phenylbutanoids: (E)-4-(2,4,5-trimethoxyphenyl)but-1,3-diene and (E)-4-(2,4,5-trimethozypheny)but-1-ene occuring in Zingiber cassumunar

(E)-4-(2',4',5'-trimethoxyphenyl)but-1,3-diene (4) and (E)-4-(2',4',5'-trimethoxyphenyl)but-1-ene (6), bioactive phenylbutanoids of Zingiber cassumunar, were synthesized exclusively with trans geometry. Treatment of methylmagnesium iodide with (E)-2',4',5'-trimethoxycinnamaldehyde (2), an oxidized product of abundantly available toxic (Z)-phenylpropanoid (1) of Acorus calamus, gave (E)-4-(2',4',5'-trimethoxyphenyl)but-3-en-2-ol (3) which upon dehydration with copper sulphate/silica gel under microwave irradiation for 3 min afforded 4 in 58% yield. Further, catalytic hydrogenation of 4 with 10% Pd/C afforded 4-(2',4',5'-trimethoxyphenyl)butane (5) which upon dehydrogenation with DDQ/SiO2 afforded hypolipidemic 6 in 54% yield.     

A mild and efficient stereoselective synthesis of (Z)- and (E)-allyl sulfides and potent antifungal agent, (Z)-3-(4-methoxybenzylidene)thiochroman-4-one from Morita-Baylis-Hillman acetates

A facile stereoselective synthesis of (Z)- and (E)-allyl sulfides has been accomplished from Morita-Baylis-Hillman acetates in one-pot by treatment with benzene thiol in the presence of catalytic amounts of 15% aqueous NaOH and TBAI in DMSO at room temperature. The method has been applied for the synthesis of (Z)-3-(4-methoxybenzylidene)thiochroman-4-one, a potent antifungal compound.     

The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary amines.

A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7. The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an aglycone of osmundalin. On the other hand, the directly conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5-hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.     

Bioactive saponins and glycosides. XXIII. Triterpene saponins with gastroprotective effect from the seeds of Camellia sinensis--theasaponins E3, E4, E5, E6, and E7

The saponin fraction from the seeds of the tea plant [Camellia sinensis (L.) O. KUNTZE (Theaceae)] was found to exhibit potent protective effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats. Five new triterpene saponins, theasaponins E3 (1), E4 (2), E5 (3), E6 (4), and E7 (5), were isolated together with 11 known saponins from the saponin fraction. The chemical structures of 1-5 were elucidated on the basis of chemical and physicochemical evidence. Among the isolated saponins, theasaponins E1 (6), E2 (7), and E5 (3) and assamsaponin C (10) showed an inhibitory effect on ethanol-induced gastric mucosal lesions at a dose of 5.0 mg/kg, p.o. and their activities were stronger than that of omeplazole. With regard to the structure-activity relationships of theasaponins, the following structural requirements for a protective effect on ethanol-induced gastric lesions were suggested; 1) the 21- and/or 22-acyl groups are essential for the activity, 2) acetylation of the 16-hydroxyl group reduce the activity.     

松毛虫性信息素(5Z,7E)-十二碳二烯醇的立体选择性合成

从简单原料乙炔出发,通过炔对丙烯醛的加成反应得到7-溴代-(4Z,6E)-庚二烯醛,再经乙二醇保护、Pd催化偶联、水解、Wittig反应和还原等步骤,立体选择性地得到松毛虫性信息素(5Z,7E)-十二碳二烯醇,其结构通过IR,NMR和MS等技术得到确认.     

Synthesis of new poly(propylenimine) dendrimers DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)](n) [n=4, 8, 16, 32, 64] functionalized with alkoxycarbonylcyclopentadienyl complexes of rhodium(I)

The reaction between [Rh[C5H4CO2(CH)2OH](NBD)] (1) and 1,1'-carbonyldiimidazole (CDI) leads to the new CO2-imidazole functionalized alkoxycarbonylcyclopentadienyl complex [Rh[C5H4CO2(CH2)2O2C-Im](NBD)] (2) (Im=imidazole). The latter was treated with five generations of poly(propylenimine) dendrimers DAB-dendr-(NH2)(n) [n=4, 8, 16, 32, 64] (DAB=diaminobutane) to accomplish the synthesis of the new organometallic dendritic macromolecules DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)](n) [n=4 (4), 8 (5), 16 (6), 32 (7), 64 (8)] based on flexible poly(propylenimine) dendrimer cores, built up to the fifth generation. Spectroscopic characterization of all the new compounds will be presented and discussed.     

（E）-1-[4-（2-hydroxy-5-methoxybenzylideneamino）-phenyl]ethanone and （E）-1-[4-（2-hydroxy-4-methoxybenzylideneamino） phenyl]ethanone：X-ray and DFT-calculated structures

The isomeric structures of(E)-1-[4-(2-hydroxy-5-methoxybenzylideneamino)-phenyl] ethanone(I) and(E)-1-[4-(2-hydroxy-4-methoxybenzylideneamino) phenyl]ethanone(Ⅱ) ,both C16H15NO3,have been determined using X-ray diffraction techniques and characterized by IR,and their molecular structures have also been optimized at the B3LYP/6-31G(d,p) level using density functional theory(DFT) . The energetic behaviors of the title compounds in solvent media have been examined using B3LYP method with the 6-31G(d,p) basis set by applying the polarizable continuum model(PCM) . The total energies of the title compounds decrease with the increasing polarity of the solvent. In addition,DFT calculations of the title compounds' molecular electrostatic potentials(MEP) were performed at the B3LYP/6-31G(d,p) level of theory. X-ray study shows that the title compounds both have strong intramolecular O-H…N hydrogen bonds. The molecules of Ⅰ are linked into a one-dimensional framework structure by C-H…π interactions,while in Ⅱ,intermolecular π···π interactions result in the formation of infinite chains running along the [010].     

Highly enantioselective aldol reaction of acetaldehyde and isatins only with 4-hydroxydiarylprolinol as catalyst: concise stereoselective synthesis of (R)-convolutamydines B and E, (−)-donaxaridine and (R)-chimonamidine

A highly enantioselective aldol reaction of acetaldehyde and a wide scope of isatins has been presented only using readily available 4-hydroxydiarylprolinol as catalyst, affording various desired 3-substituted 3-hydroxyindolin-2-one adducts with moderate to high yield (up to 95%) and good enantioselectivities (up to 98% ee). This method not only represents an example of concise stereoselective synthesis of enantiopure (R)-convolutamydines B and E, but also firstly exhibits expedient asymmetric synthesis optically active (−)-donaxaridine and (R)-chimonamidine.     

On the viability of small endohedral hydrocarbon cage complexes: X@C4H4, X@C8H8, X@C8H14, X@C10H16, X@C12H12, AND X@C16H16

Small hydrocarbon complexes (X@cage) incorporating cage-centered endohedral atoms and ions (X = H(+), H, He, Ne, Ar, Li(0,+), Be(0,+,2+), Na(0,+), Mg(0,+,2+)) have been studied at the B3LYP/6-31G(d) hybrid HF/DFT level of theory. No tetrahedrane (C(4)H(4), T(d)()) endohedral complexes are minima, not even with the very small hydrogen atom or beryllium dication. Cubane (C(8)H(8), O(h)()) and bicyclo[2.2.2]octane (C(8)H(14), D(3)(h)()) minima are limited to encapsulating species smaller than Ne and Na(+). Despite its intermediate size, adamantane (C(10)H(16), T(d)()) can enclose a wide variety of endohedral atoms and ions including H, He, Ne, Li(0,+), Be(0,+,2+), Na(0,+), and Mg(2+). In contrast, the truncated tetrahedrane (C(12)H(12), T(d)()) encapsulates fewer species, while the D(4)(d)() symmetric C(16)H(16) hydrocarbon cage (see Table of Contents graphic) encapsulates all but the larger Be, Mg, and Mg(+) species. The host cages have more compact geometries when metal atoms, rather than cations, are inside. This is due to electron donation from the endohedral metals into C-C bonding and C-H antibonding cage molecular orbitals. The relative stabilities of endohedral minima are evaluated by comparing their energies (E(endo)) to the sum of their isolated components (E(inc) = E(endo) - E(cage) - E(x)) and to their exohedral isomer energies (E(isom) = E(endo) - E(exo)). Although exohedral binding is preferred to endohedral encapsulation without exception (i.e., E(isom) is always exothermic), Be(2+)@C(10)H(16) (T(d)(); -235.5 kcal/mol), Li(+)@C(12)H(12) (T(d)(); 50.2 kcal/mol), Be(2+)@C(12)H(12) (T(d)(); -181.2 kcal/mol), Mg(2+)@C(12)H(12) (T(d)(); -45.0 kcal/mol), Li(+)@C(16)H(16) (D(4)(d)(); 13.3 kcal/mol), Be(+)@C(16)H(16) (C(4)(v)(); 31.8 kcal/mol), Be(2+)@C(16)H(16) (D(4)(d)(); -239.2 kcal/mol), and Mg(2+)@C(16)H(16) (D(4)(d)(); -37.7 kcal/mol) are relatively stable as compared to experimentally known He@C(20)H(20) (I(h)()), which has an E(inc) = 37.9 kcal/mol and E(isom) = -35.4 kcal/mol. Overall, endohedral cage complexes with low parent cage strain energies, large cage internal cavity volumes, and a small, highly charged guest species are the most viable synthetic targets.