Highly oxygenated bisabolenes and an acetylene from Matricaria aurea.

Reinvestigation of the aerial parts of Matricaria aurea led to the isolation of three new bisabolenes and a new acetylene. The structures of the four compounds, namely (1R*,2R*,3R*,6R*,7R*)1,2,3,6,7- pentahydroxy-bisabol-10(11)-ene, (1R*,2R*,3R*,6R*,7R*)1,2,3,6,7-pentahydroxy-1-acetoxy-bisabol-10(1 1)-ene, (1R*,2R*,3R*,6R*,7R*)1,2,3,6,7-pentahydroxy-2-acetoxy-bisabol-10(1 1)-ene and (3S*,4S*,5R*)-(E)-3,4-dihydroxy-2-(hexa-2,4-diynyliden)-1,6- dioxaspiro-(4,5)decane, were deduced from the high field NMR studies.     

Three sesquiterpene hydrocarbons from the roots of Panax ginseng C.A. Meyer (Araliaceae)

The volatile constituents of the roots of Panax ginseng C.A. Meyer have been investigated after hydrodistillation and analysed by means of different analytical methods. Besides several compounds already known three sesquiterpene hydrocarbons have been isolated from the essential oil. Structure elucidation of the bicyclic panaxene as well as of the tricyclic panaginsene and ginsinsene was performed by MS and NMR. They have been identified as (1R*,2S*,5S*)-2-ethenyl-1(1-methylethenyl)-2,6,6-trimethylbicyclo[3.2.0]heptane (panaxene), (1S*,8S*,11R*)-4,7,7,11-tetramethyltricyclo[6.3.0.0(1,5)]undec-4-ene (panaginsene) und (1R*,6R*,7R*)-3,7,10,10-tetramethyltricyclo[4.3.2.0(2,6)]undec-2-ene (ginsinsene).     

Oxygenated lycopene and dehydrated lutein in tomato puree

Oxygenated lycopenes, (2S*,5S*,6R*)-2,6-cyclolycopene-1-methoxy-5-ol, (2S*,5S*,6R*)-1,16-didehydro-2,6-cyclolycopene-5-ol and (3R,6'R)-3-hydroxy-3',4'-didehydro-beta,gamma-carotene (anhydrolutein I) were isolated from tomato puree. The structures of these compounds were elucidated on the basis of spectroscopic evidence.     

Synthesis of (-)-methyl shikimate via enzymatic resolution of (1S*, 4R*, 5R*)-4-hydroxy-6-oxabicyclo[3.2.1]oct-2-en-7-one.

The synthesis of methyl (-)-shikimate [(-)-2] was achieved via lipase-catalyzed optical resolution of (1S*, 4R*, 5R*)-4-hydroxy-6-oxabicyclo[3.2.1]oct-2-en-7-one (3). Transesterification of (+/-)-3 and vinyl acetate with lipase MY and subsequent hydrolysis gave optically pure (-)-3. This compound was converted to (-)-2 in two steps.     

(1S,3S,7R)-3-methyl-alpha-himachalene from the male sandfly Lutzomyia longipalpis (Diptera: Psychodidae) induces neurophysiological responses and attracts both males and females

Lutzomyia longipalpis adult males form leks on or near hosts and release (1S,3S,7R)-3-methyl-alpha-himachalene from their tergal glands to lure females to the same site for mating and feeding. Here we have examined whether the male-produced attractant could also serve as a male aggregation stimulus. High resolution chiral capillary gas chromatography analysis of male tergal gland extracts, synthetic (1S,3S,7R)-3-methyl-alpha-himachalene, and a synthetic mixture of all isomers of 3-methyl-alpha-himachalene, was coupled to electrophysiological recordings from ascoid sensillum receptor cells in antennae of male and female sandflies. Receptor cells of both sexes responded only to the main component of the male tergal gland extract that eluted at the same retention time as (1S,3S,7R)-3-methyl-alpha-himachalene. Furthermore, of the eight 3-methyl-alpha-himachalene isomers in the synthetic mixture only the fraction containing (1S,3S,7R)-3-methyl-alpha-himachalene, co-eluting with an isomer of (1S*,3S*,7S*)-3-methyl-alpha-himachalene, elicited an electrophysiological response from male and female ascoid sensillum receptor cells. Both males and females flew upwind in a wind tunnel towards a filter paper disk treated with either 4-6 male equivalents of the tergal gland extract, pure (1S,3S,7R)-3-methyl-alpha-himachalene or the synthetic mixture of eight isomers. This indicates that (1S,3S,7R)-3-methyl-alpha-himachalene derived from L. longipalpis males may have a dual function in causing male aggregation as well as serving as a sex pheromone for females.     

Influence on Insecticidal Activity of the 3-(3,4-Methylenedioxyphenyl) Group in the 1,4-Benzodioxanyl Moiety of Haedoxan

The influence on the insecticidal activity of haedoxan A of its 3-(3,4-methylenedioxyphenyl) group in the 1,4-benzodioxanyl moiety was examined with two (±)-(1S*,2R*,5R*,6S*)-6-[(2R*,3R*)-3-alkyl-6- methoxy-2-methoxymethyl-1,4-benzodioxan-7-yl]-2-(2,6-dimethoxyphenoxy)-1-hydroxy-3,7-dioxabicyclo-[3.3.0]octanes. Replacement of the methylenedioxyphenyl group of haedoxan by methyl and n-butyl group resulted in a large decrease in the activity, indicating the importance of the 3-aryl group for the potent insecticidal activity of haedoxan.     

New chemical constituents from the endophyte Streptomyces species LR4612 cultivated on Maytenus hookeri

From solid cultures of the biologically important endophyte Streptomyces species LR4612, cultivated on Maytenus hookeri, four new and two known compounds were isolated. The new compounds were identified as (2S*,3S*)-5-amino-3-hydroxy-5-oxopentan-2-yl 3-(formylamino)-2-hydroxybenzoate (1), N-[(3R*,4R*)-3-amino-3,4-dihydro-4-methyl-2,6-dioxo-2H,6H-1,5-benzodioxocin-10-yl]formamide (2), (5beta,6alpha)-6,11-dihydroxyeudesmane (3), and 5-(6,7-dihydroxy-6-methyloctyl)furan-2(5H)-one (4); the known compounds were elucidated as sorbicillin (5) and N-acetyltyramine (6). The structures were established by HR-ESI-MS and in-depth NMR analyses.     

Clerodane-type diterpenes from the seed pods of Hymenaea courbaril var. stilbocarpa.

Three known and two new diterpenes were isolated from the ethyl acetate extract of Hymenaea courbaril var. stilbocarpa seed pods. One of the compounds was elucidated as (5R*,8S*,9S*,10R*)-cleroda-3,13E-dien-15-oic acid and the other was elucidated, after treatment with diazomethane, as methyl (5S*,8S*,9S*,10R*)-cleroda-3,13E-dien-15-oate. The known diterpenes were identified as (-)-ozic acid, (-)-isoozic acid and (-)-kovalenic acid which were characterized as their methyl ester derivatives.     

Synthesis and stereostructure-activity relationship of three asymmetric center pyrethroids: 2-methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether and cyanohydrin ester

2-Methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether 2 and cyanohydrin ester 3, a couple of pyrethroids with three asymmetric centers, were synthesized. Of each of the four diastereomers of 2 and 3, only the (1R*,2R*,3R*)-2a and 3a showed significant insecticidal activities. Dual sets of enantiomers [(1R,2R,3R)-(-)-2a and (1S,2S,3S)-(+)-2a] and [(1R,2R,3R)-(-)-3a and (1S,2S,3S)-(+)-3a] were synthesized through the asymmetric cyclopropanation using the Aratani catalyst. Significant separations of insecticidal activities were observed between both the enantiomers against the tobacco cutworm (Spodoptera litura) and the common mosquito (Culex pipiens pallens); (1S,2S,3S)-(+)-2a and (+)-3a showed higher activities than their antipodes (1R,2R,3R)(-)-2a and (-)-3a. This result is the second example of such synthetic pyrethroids with three asymmetric centers.     

Alkyl phenols and derivatives from Tapirira obtusa

From the bark of Tapiria obtusa, six alkyl phenol derivatives were isolated: 1-hydroxy-3-[(Z)-7'-nonadecenyl]-benzene, 1-hydroxy-3-[(Z)-7'-heptadecenyl]-benzene, 1-hydroxy-3-[14'-phenyltetradecyl]-benzene, and 1-hydroxy-3-[16'-phenyltetradecyl]-benzene, and their possible biogenetic precursors, 1-(16'-phenyl-12'Z-hexadecenyl)-4-Z-cyclohexene-(1S*,3S*)-diol and (4S*,6S*)-dihydroxy-6-(14'Z-nonadecenyl)-2-cyclohexenone. The structures of these compounds were elucidated by chemical and spectroscopic analysis, (4S*,6S*)-Dihydroxy-6-(14'Z-nonadecenyl)-2-cyclohexenone showed cytotoxic activity.     

Acetyl-CoA carboxylase inhibitors from avocado (Persea americana Mill) fruits

A methanol extract of avocado fruits showed potent inhibitory activity against acetyl-CoA carboxylase, a key enzyme in fatty acid biosynthesis. The active principles were isolated and identified as (5E,12Z,15Z)-2-hydroxy-4-oxoheneicosa-5,12,15-trienyl (1), (2R,12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dienyl (2), (2R*,4R*)-2,4-dihydroxyheptadec-16-enyl (3) and (2R*,4R*)-2,4-dihydroxyheptadec-16-ynyl (4) acetates by instrumental analyses. The IC50 of the compounds were 4.0 x 10(-6), 4.9 x 10(-6), 9.4 x 10(-6), and 5.1 x 10(-6) M, respectively.     

Versatile precursor to ruthenium-bis(phosphine) hydrogenation catalysts

The known complex trans-RuCl2(NBD)Py2 (1, NBD is norbornadiene, Py is pyridine) reacts with either (R)-BINAP ((R)-2, 2'-bis(diphenylphosphino)-1,1'-binaphthyl), (S;S)-Chiraphos ((2S;3S-(-)-2,3-bis(diphenylphosphino)butane), (S;S)-Skewphos ((2S;4S)-(-)-2,4-bis(diphenylphosphino)pentane), (R)-(S)-Josiphos ((R)-(-)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylpho sphine), (R;R)-Norphos ((2R;3R)-(-)-2, 3-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene), or (R;R)-Me-DUPHOS ((-)-1,2-bis((2R;5R)-2, 5-dimethylphospholano)benzene) to generate in high yields the crystalline complexes trans-RuCl2(P-P*)Py2 (P-P* is the corresponding chiral bis(phosphine)). The complexes trans-RuCl2(P-P*)Py2 are active enantioselective hydrogenation catalysts for ketoesters and noncarboxylic olefins in the presence of small amounts of HBF4 (aq.). They are active for hydrogenation of carboxylic substrates in the presence of Et3N. Reaction of trans-RuCl2(P-P*)Py2 with (rac)-1,2-diphenylethylene-diamine (N-N*, either enantiomer) forms in good yields the corresponding compounds trans-RuCl2(P-P*)(N-N*). Representative hydrogenations with these catalysts are presented.     

Synthesis of new chiral bis(isoxazoline) ligands containing spiro[5.5]undecane skeleton

New chiral bis(isoxazoline) ligands bearing a spiro[5.5]undecane skeleton were designed and synthesized in five steps from diethyl malonate (3). These ligands showed a coordinating ability to Cu(II) as chiral ligands. A complex of (+)-(M*,S*,R*)-[5.5]-SPRIX 2b and Cu(OTf)(2) catalyzed the conjugate addition of diethyl-zinc to 2-cyclohexenone (8) to give (S)-3-ethyl-cyclohexanone (9) in 93% yield with 54% ee.     

(2R*, 3S*)-1-[18F]fluoro-2,3-bis(4-hydroxyphenyl)pentane [( 18F]fluoronor-hexestrol), a positron-emitting estrogen that shows highly-selective, receptor-mediated uptake by target tissues in vivo

The positron-emitting, non-steroidal estrogen (2R*, 3S*)-1-[18F]fluoro-2,3-bis(4-hydroxyphenyl)pentane [( 18F]-fluoronor-hexestrol), has been prepared by fluoride ion displacement on a labile trifluoromethanesulfonate (triflate) derivative of a suitably protected precursor, followed by removal of the aryl triflate groups with lithium aluminum hydride and purification by HPLC. In immature female rats, this compound is taken up selectively by the uterus and is retained for prolonged periods, due to its binding to the estrogen receptor. This compound and related 18F-labeled estrogens thus appear to be promising agents for imaging estrogen receptor-positive breast tumors in humans.     

L-649,923, sodium (beta S*, gamma R*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propylthio)- gamma-hydroxy-beta-methylbenzenebutanoate, a selective, orally active leukotriene receptor antagonist

L-649,923, Sodium (beta S*, gamma R*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)- gamma- hydroxy-beta-methylbenzenebutanoate is a selective and competitive inhibitor of [3H]leukotriene D4 (Ki value of 400 nM) and to a lesser extent [3H]leukotriene C4 (Ki value of 8.6 microM) binding in guinea-pig lung homogenates. Functionally, it selectively antagonized contractions of guinea pig trachea induced by leukotriene C4, D4, E4, and F4 but not those induced by acetylcholine, histamine, serotonin, prostaglandin F2 alpha, or U-44069 (stable endoperoxide analogue). Schild plot analysis indicated a competitive inhibition of contractions of guinea-pig ileum induced by leukotriene D4 (pA2 8.1) and contractions of guinea-pig trachea induced by leukotrienes E4 and F4 (pA2 7.1 and 6.9, respectively). In contrast, contractions of guinea-pig trachea induced by leukotrienes C4 (pA2 7.2; slope 0.6) and D4 (pA2 7.2; slope 0.7) were inhibited in a noncompetitive fashion. In vivo, intravenously administered L-649,923 selectively blocked bronchoconstriction induced in anesthetized guinea pigs by leukotriene C4 and D4 (ED50 values i.v. 0.38 and 0.26 mg/kg, respectively) but not that induced by histamine, arachidonic acid, serotonin, U-44069, or acetylcholine. Following intraduodenal administration, L-649,923, blocked leukotriene D4 induced bronchoconstriction (5 and 10 mg/kg). The present findings indicate that selective antagonists, such as L-649,923, may be useful for defining the role of leukotrienes in diseases such as bronchial asthma.     

Jatropham derivatives and steroidal saponins from the bulbs of Lilium hansonii.

Two new jatropham derivatives and three new steroidal saponins were isolated from the fresh bulbs of Lilium hansonii, along with previously known compounds. The structures of the new compounds were elucidated, on the basis of spectroscopic data and chemical evidence, and by comparing them with those of known compounds, as (-)-5-hydroxy-3-methyl-3-pyrrolin-2-one (jatropham) 5-O-beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranoside, (2S*,4R*)-1-(3-methyl-2-oxo-3-pyrrolinyl)-4-methyl-5-oxo-2-pyrr olidinecarboxyli c acid, 26-O-beta-D-glucopyranosyl-(25R)-5 alpha-furostan-3 beta,22 zeta-diol 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl-(1----4)]- beta-D-glucopyranoside, (25R)-5 alpha-spirostan-3 beta,12 alpha-diol 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl-(1----4)]- beta-D-glucopyranoside and (25R)-spirost-5-en-3 beta,12 alpha-diol 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl-(1----4)]- beta-D-glucopyranoside, respectively. The stereostructure of jatropham dimer, the plain structure of which was presented previously, was confirmed by X-ray crystallographic analysis. The inhibitory activity on cyclic AMP phosphodiesterase of the steroidal saponins was evaluated.     

Chemical and genetic diversity of Ligularia latihastata and Ligularia villosa in Yunnan Province of China

The chemical constituents of the root extracts and the nucleotide sequences of the atpB-rbcL intergenic region of Ligularia latihastata and L. villosa, collected in northwestern Yunnan Province, were studied. In the twelve collected samples of L. latihastata, two major benzofurans, 5,6-dimethoxy-2-(1-methylethenyl)-1-benzofuran (1) and euparin (2) were detected as major components. The minor compound (2R*,3S*)-5-acetyl-2,3-dihydro-6-hydroxy-2-(1-methylethenyl)-1-benzofuran-3-yl (2Z)-2-[(acetoxy)methyl]but-2-enoate (4) was found to be susceptible to artifact formation upon extraction with EtOH. The intra-specific diversity in chemical composition of the samples was small, but the diversity in the atpB-rbcL sequence was fairly large. Compounds 1 and 2 were also found in the three collected samples of L. villosa, indicating that the two species are chemically close to each other, in agreement with morphological taxonomy.     

Utilizing hydrolases of opposite enantiopreference for the preparation of both enantiomers of (1R,7aR)-(-)- and (1S,7aS)-(+)-3,6,7,7a-tetrahydro-1-hydroxy-7a-methyl-1H-inden-5(2H)-one

Four racemic esters of (1R*,7aR*)-3,6,7,7a-tetrahydro-1-hydroxy-7a-methyl-1H-inden-5(2H)-one were prepared and subjected to hydrolysis with two types of hydrolases, including alcalase and three lipases. Alcalase and lipase showed opposite enantiopreference on these esters. Based on this result, we developed a gram-scale procedure using butanoate as the substrate, which was treated consecutively with alcalase and lipase from Candida rugosa (CRL), to give both enantiomers of the title compound in high yields and high enantiomeric excess.     

1,2-Silyl-migrative cyclization of vinylsilanes bearing an amino group

In the presence of an acid catalyst, alpha-alkyl-substituted (Z)-vinylsilanes 1, bearing a tosylamino group, were smoothly cyclized to trans-2-alkyl-3-silylpiperidines 2 (1,2-silyl-migration products) and (2R*, 1'S*)-2-(1'-silylalkyl)pyrrolidines 3. The elaboration of the reaction conditions enabled the selective preparation of each cyclized product. The acid-catalyzed cyclization of (Z)-vinylsilane 5, whose methylene tether is shorter than that of 1 by one carbon, formed only the 1,2-silyl-migration product 6 with high trans-selectivity. These cyclizations were found to proceed in a stereospecific manner.