Synthesis of (2s, 3r, 7rs)-stegobinone [2,3-dihydro-2,3,5-trimethyl-6-(1-methyl-2- oxobutyl)-4h-pyran-4-one] and its (2r, 3s, 7rs)-isomer : The pheromone of the drugstore beetle

Reaction of acetaldehyde with the trianion of 4,6-dimethylnonane-3,5,7-trione followed by acidification yielded a stereoisomeric mixture of stegobinone, the pheromone of Stegobium paniceum L. Acylation of the dianion derived from 4-methylheptane-3,5-dione with a mixed anhydride prepared from (2R, 3S)-3-hydroxy-2-methylbutanoic acid or its enantiomer led to (2S,3R,7RS)- or (2R, 3S, 7RS)-stegobinone. The natural pheromone possesses (2S,3R)-stereochemistry.     

Absolute Configuration of Multifidene and Viridiene,the Sperm Releasing and Attracting Pheromones of Brown Algae

The absolute configurations of the two algal pheromones multifidene 1 and viridiene 2 were determined as (+)-(3S, 4S)-3-[(Z)-1-butenyl]-4-vinylcyclopentene and (+)-(3R, 4S)-3-[(1Z)-1, 3-butadienyl]-4-vinylcyclopentene, respectively. The strategy involves enzyme-initiated asymmetric synthesis of the ring-saturated pheromone analogues (+)- 8a and (?)- 8b and their subsequent catalytic hydrogenation to the chiral cycloalkanes 9a and 9b , only the letter of which is also obtained from the two natural messengers (+)- 1 or (+)- 2 . Biological activity assays proved these enantiomers of 1 or 2 to be the characteristic pheromones for male gametes of the seaweeds Syringoderma, Cutleria multifida and Chorda tomentosa.     

Synthesis and pharmacological effects of optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]-ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride

Optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate [(S)-(+)-1 and (R)-(-)-1] hydrochlorides were synthesized with high optical purities from (R)-(-)- and (S)-(+)-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)- 3-pyridinecarboxylic acids [(R)-(-)-6 and (S)-(+)-6], which are available from (+/-)-6 by optical resolution using quinidine and cinchonidine, respectively. From pharmacological investigations of (S)-(+)-1 and (R)-(-)-1 such as the antihypertensive effect on spontaneously hypertensive rats and inhibition of [3H]nimodipine binding to rat cardiac membrane homogenate, the active form of 1 was defined to be the (4S)-(+)-enantiomer of 1.     

(Fluoren-9-ylidene)methanedithiolato complexes of gold: synthesis, luminescence, and charge-transfer adducts

Piperidinium 9H-fluorene-9-carbodithioate and its 2,7-di-tert-butyl-substituted analogue [(pipH)(S(2)CCH(C(12)H(6)R(2)-2,7)), R = H (1a), t-Bu (1b)] and 2,7-bis(octyloxy)-9H-fluorene-9-carbodithioic acid [HS(2)CCH(C(12)H(6)(OC(8)H(17))(2)-2,7), 2] and its tautomer [2,7-bis(octyloxy)fluoren-9-ylidene]methanedithiol [(HS)(2)C=C(C(12)H(6)(OC(8)H(17))(2)-2,7), 3] were employed for the preparation of gold complexes with the (fluoren-9-ylidene)methanedithiolato ligand and its substituted analogues. The gold(I) compounds Q(2)[Au(2)(mu-kappa(2)-S,S-S(2)C=C(C(12)H(6)R(2)-2,7))(2)], where Q(+) = PPN(+) or Pr(4)N(+) for R = H (Q(2)4a) or Q(+) = Pr(4)N(+) for R = OC(8)H(17) [(Pr(4)N)(2)4c], were synthesized by reacting Q[AuCl(2)] with 1a or 2 (1:1) and excess piperidine or diethylamine. Complexes of the type [(Au(PR'3))(2)(mu-kappa(2)-S,S-S(2)C=C(C(12)H(6)R(2)-2,7))(2)] with R = H and R' = Me (5a), Et (5b), Ph (5c), and Cy (5d) or R = t-Bu and R' = Me (5e), Et (5f), Ph (5g), and Cy (5h) were obtained by reacting [AuCl(PR'(3))] with 1a,b (1:2) and piperidine. The reactions of 1a,b or 2 with Q[AuCl(4)] (2:1) and piperidine or diethylamine gave Q[Au(kappa(2)-S,S-S(2)C=C(C(12)H(6)R(2)-2,7))(2)] with Q(+) = PPN(+) for R = H [(PPN)6a], Q(+) = PPN(+) or Bu(4)N(+) for R = t-Bu (Q6b), and Q(+) = Bu(4)N(+) for R = OC(8)H(17) [(Bu(4)N)6c]. Complexes Q6a-c reacted with excess triflic acid to give [Au(kappa(2)-S,S-S(2)C=C(C(12)H(6)R(2)-2,7))(kappa(2)-S,S-S(2)CCH(C(12)H(6)R(2)-2,7))] [R = H (7a), t-Bu (7b), OC(8)H(17) (7c)]. By reaction of (Bu(4)N)6b with PhICl(2) (1:1) the complex Bu(4)N[AuCl(2)(kappa(2)-S,S-S(2)C=C(C(12)H(6)(t-Bu)(2)-2,7))] [(Bu(4)N)8b] was obtained. The dithioato complexes [Au(SC(S)CH(C(12)H(8)))(PCy(3))] (9) and [Au(n)(S(2)CCH(C(12)H(8)))(n)] (10) were obtained from the reactions of 1a with [AuCl(PCy(3))] or [AuCl(SMe(2))], respectively (1:1), in the absence of a base. Charge-transfer adducts of general composition Q[Au(kappa(2)-S,S-S(2)C=C(C(12)H(6)R(2)-2,7))(2)].1.5TCNQ.xCH(2)Cl(2) [Q(+) = PPN(+), R = H, x = 0 (11a); Q(+) = PPN(+), R = t-Bu, x = 2 (11b); Q(+) = Bu(4)N(+), R = OC(8)H(17), x = 0 (11c)] were obtained from Q6a-c and TCNQ (1:2). The crystal structures of 5c.THF, 5e.(2)/(3)CH(2)Cl(2), 5g.CH(2)Cl(2), (PPN)6a.2Me(2)CO, and 11b were solved by X-ray diffraction studies. All the gold(I) complexes here described are photoluminescent at 77 K, and their emissions can be generally ascribed to LMMCT (Q(2)4a,c, 5a-h, 10) or LMCT (9) excited states.     

人工蜂王的研制及对东方蜜蜂的生物活性

本文模拟天然蜂王信息素的组成，将合成的９－氧代－２Ｅ－癸烯酸（蜂王物质，ＱｕｅｅｎＳｕｂｓｔａｎｃｅ）、Ｒ／Ｓ－９－羟基－２Ｅ－癸烯酸（臭味抑制剂，Ｓｔｉｎｋ－ｏｄｏｕｒｉｎｈｉｂｉｔｏｒ）及其它一些微量成分按一定的比例混合，并附于醋酸纤维上制成人工蜂王，运用人工蜂王对东方蜜蜂进行了活性测试，结果表明在群味、聚集、消除失王情绪、抑制工蜂产卵、抑制建造急造王台等方面表现出了显著的生物活性，同时也研究了人工蜂王对产蜜量的影响。     

Chiral monomeric and homochiral dimeric copper(II) complexes of a new chiral ligand, N-(1,2-bis(2-pyridyl)ethyl)pyridine-2-carboxamide: an example of molecular self-recognition

Reaction of Cu(ClO(4))(2) x 6H(2)O with a racemic mixture of the novel chiral ligand N-(1,2-bis(2-pyridyl)ethyl)pyridine-2-carboxamide (PEAH) affords only the homochiral dimeric copper(II) complexes [Cu(2)((R)()PEA)(2)](ClO(4))(2) and [Cu(2)((S)()PEA)(2)](ClO(4))(2) in a 1:1 ratio. The phenomenon of molecular self-recognition is also observed when a racemic mixture of the monomeric copper(II) complex [Cu((R(S))()PEA)(Cl)(H(2)O)] is converted into the homochiral dimeric species [Cu(2)((R(S))()PEA)(2)](ClO(4))(2) via reaction with Ag(+) ion. This is the first report of direct conversion of a racemic mixture of a chiral monomeric copper(II) complex to a mixture of the homochiral dimers.     

Synthesis of chiral 1,2-diols and related compounds of biological activities via stepwise ring fission of 5-alkyl-6,8-dioxabicyclo[3.2.1]octane skeleton

5-Alkyl-7-mesyloxymethyl-6,8-dioxabicyclo[3.2.1]octanes , prepared from (+)-tartaric acid, were converted by means of an organoaluminium reagent Et₂AlSPh into the pyranoid monothioacetals, which were utilized via the successive thioacetalization to the synthesis of the insect pheromones (+)-disparlure and (−)-(2S,3S)-octanediol.     

Synthesis of the (r)(-)enantiomers of the pheromone components of several species of trogoderma [coleoptera: dermestidae]

The chemically pure (R)(-)-enantiomers of (Z)- and (E)-14-methyl-8-hexadecen-1-ol and of (Z)- and (E)-14-methyl-8-hexadecenal, which are sex pheromone components of several species of female dermestid beetles, were synthesised in fairly good overall yield and in rather high optical purity starting from (S)(-)-citronellol. A mixture of (R)(Z)- and (R)(E)-14-methyl-8-hexadecenal in the 92:8 ratio was 10⁷ time less active than a mixture of the corresponding (S)-enantiomers when tested on male Khapra beetles, Trogoderma granarium.     

Biosynthese der Verrucarine und Roridine. Teil 5. Synthese von zwei Diastereoisomerenpaaren des [1,8-14C]-α-Bisabolols und Versuche zu deren Einbau in Verrucarol Verrucarine und Roridine, 32. Mitteilung [1]

The diastereoisomeric (+)-[1,8-¹⁴C]-(1'R,6R, S)-α-bisabolol ( 2a ) and (?)-[1,8-¹⁴C]-(1′S, 6R, S)-α-bisabolol ( 2b ) were synthesized by reaction of the Grignard compound of [1,6-¹⁴C]-5-bromo-2-methyl-2-pentene ( 12 ) with (+)-(R)- and (?)-(S)-4-acetyl-1-methyl-1-cyclohexene, ( 6a ) and ( 6b ) respectively. For the preparation of compound 12, cyclopropyl methyl ketone was treated with [¹⁴C]-methyl magnesium iodide to form the carbinol 11, which was cleaved by HBr. Compounds 6a and 6b were synthesized from (+)-(R)- and (?)-(S)-limonene, ( 4a ) and ( 4b ), via the derivatives 5a , 6a and 5b , 6b respectively. - This synthesis established the absolute configuration at C(1′) of the natural α-bisabolols: (R) for (+)-α-bisabolol and (S) for (?)-α-bisabolol. - Feeding experiments with cultures of Myrothecium roridum and radioactive (+)-(1′R, 6R, S)- and (?)-(1′S, 6R, S)-α-bisabolol ( 2a ) and ( 2b ) gave negative results. These findings indicate that bisabolane derivatives are not intermediates in the biosynthesis of verrucarol (3).     

Stereoselective Synthiesis of Both Enantiomers of Disparlure from D-Glucose

D-Glucose was transformed stereoselectively into (7R,8S)8-benzyloxy-7-hydroxy-2-methyl-9-octadecene from which both enantiomers of disparlure, (7R,8S)-(+)-and (7S,8R)-(-)-7,8-epoxy-2-methyloctadecane, sex pheromone of the gypsy moth, were obtained in four and three steps, respectively.     

Ketopinic acid and diisoproylideneketogulonic acid as chiral ion-pair selectors in capillary electrophoresis. Enantiomeric impurity analysis of S-timolol and 1R,2S-ephedrine

1S,4R-(+)-ketopinic acid [(+)-KPA] has been introduced as a chiral selector for the separation of pharmacologically active amines by non-aqueous capillary electrophoresis (NACE). (+)-KPA gave enantioresolution for most of the compounds previously separated by 2R,3S,4R,5S-(-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid [(-)-DIKGA], but with a reversed migration order. A complete enantioresolution (Rs=4.2) was obtained for timolol, a compound that could not be resolved using (-)-DIKGA as the selector. Thus, (+)-KPA was evaluated for the enantiomeric purity determination of S-timolol. A method based on pre-concentration by transient isotachophoresis (tITP) provided a limit of detection (LOD) of 0.2% R-timolol in S-timolol samples. Because of the lack of enantioresolution of ephedrine when (+)-KPA was used as the selector, a method with (-)-DIKGA has been developed and validated for determination of the enantiomeric purity of the 1R,2S enantiomer. The method gave good precision and accuracy with an LOD (S/N=3) of 0.033% for the enantiomeric impurity 1S,2R-ephedrine.     

Asymmetric addition of dialkyl phosphite and diamido phosphite anions to chiral, enantiopure sulfinimines: a new, convenient route to enantiomeric α-aminophosphonic acids

Lithium or sodium dialkyl phosphites and diamido phosphites 3 undergo addition to (+)-(S)-benzylidene-p-toluenesulfinamide 2 affording N-sulfinyl-α-aminophosphonates 4 in a diastereoisomeric ratio from 63:37 to 94:6. The major diastereoisomers formed in addition of lithium dimethyl phosphite 3a and lithium bis-diethylamido phosphite 3e to (+)-(S)-2 were separated and converted into enantiopure (+)-(R)- and (−)-(S)-α-aminobenzyl phosphonic acids 5, respectively.     

Synthesis of (4R)-Methylnonan-1-ol and (4R,8RS)-Dimethyldecanal from (S)-(+)-3,7-Dimethyl-1,6-octadiene

Optically active (4R,8RS)-dimethyldecanal, an analog of the aggregation pheromone of the flour beetles Tribolium confusum and T. Castaneum, and (4R)-methylnonan-1-ol, the sex pheromone of the yellow mealworm Tenebrio molitor L., are synthesized using ozonolytic transformation of (6R,10)-dimethyl-9-undecen-2-one to (6R)-methyl-9-hydroxynonan-2-one in the key step. The starting compound is available as enantiomerically enriched (ee ~50%) (S)-(+)-3,7-dimethyl-1,6-octadiene.     

The electron-releasing homoconjugated carbonyl group. Application to the total syntheses of 3-deoxy-, 4-deoxy-hexose, lividosamine and derivatives

The regioselective electrophilic addition of benzeneselenyl bromide to (−)-(1S,4S)-7-oxabicyclo[2.2.1]-hept-5-en-2-one were exploited to develop efficient syntheses of methyl 3-deoxy--D-arabino-hexofuranoside and 4-deoxy-D-lyxo-hexopyranose. Similarly, D-lividosamine (3-deoxy-D-glucosamine) was derived from (+)-(1R,4R)-7-oxabicyclo[2.2.1]hept-5-en-2-one.     

On the reaction of Ph2PNHPPh2 with RNCS (R=Et, Ph, p-NO2C6H4): preparation of the zwitterionic ligand EtNHC(S)Ph2P==NPPh2C(S)NEt (HSNS) and the zwitterionic metalate [(SNS)Rh(CO)

The reaction of Ph(2)PNHPPh(2) (PNP) with RNCS (Et, Ph, p-NO(2)(C(6)H(4))) gives addition products resulting from the attack of the P atoms of PNP on the electrophilic carbon atom of the isothiocyanate. When PNP is reacted with EtNCS in a 1:2 molar ratio, the zwitterionic molecule EtNHC(S)PPh(2)==NP(+)Ph(2)C(S)N(-)Et (HSNS) is obtained in high yield. HSNS can be protonated (H(2)SNS(+)) or deprotonated (SNS(-)), behaving in the latter form as an S,N,S-donor pincer ligand. The reaction of HSNS with [(acac)Rh(CO)(2)] (acac=acetylacetonate) affords the zwitterionic metalate [(SNS)Rh(CO)]. Other products can be obtained depending on the R group, the PNP/RNCS ratio (1:1 or 1:2), and the reaction temperature. The proposed product of the primary attack of PNP on RNCS, Ph(2)PN==PPh(2)C(S)NHR (A), cannot be isolated. Reaction of A with another RNCS molecule leads to 1:2 addition compounds of the general formula RNHC(S)PPh(2)==NP(+)Ph(2)C(S)N(-)R (1), which can rearrange into the non-zwitterionic product RNHC(S)PPh(2)==NP(S)Ph(2) (2) by eliminating a molecule of RNC. Two molecules of A can react together, yielding 1:1 PNP/RNCS zwitterionic products of the formula RNHCH[PPh(2)==NP(S)Ph(2)]PPh(2)==NP(+)Ph(2)C(S)N(-)R (3). Compound 3 can then rearrange into RNHCH[PPh(2)==NP(S)Ph(2)](2) (4) by losing a RNC molecule. When R=Et (a), compounds 1 a, 2 a (HSNS), and 4 a have been isolated and characterized. When R=Ph (b), compounds 2 b and 4 b can be prepared in high yield. When R=p-NO(2)C(6)H(4) (c), only compound 3 c is observed and isolated in high yield. The crystal structures of HSNS, [(SNS)Rh(CO)], and of the most representative products have been determined by X-ray diffraction methods.     

Stereospecificity of the dehydratase domain of the erythromycin polyketide synthase

The dehydratase (DH) domain of module 4 of the 6-deoxyerythronolide B synthase (DEBS) has been shown to catalyze an exclusive syn elimination/syn addition of water. Incubation of recombinant DH4 with chemoenzymatically prepared anti-(2R,3R)-2-methyl-3-hydroxypentanoyl-ACP (2a-ACP) gave the dehydration product 3-ACP. Similarly, incubation of DH4 with synthetic 3-ACP resulted in the reverse enzyme-catalyzed hydration reaction, giving an ～3:1 equilbrium mixture of 2a-ACP and 3-ACP. Incubation of a mixture of propionyl-SNAC (4), methylmalonyl-CoA, and NADPH with the DEBS β-ketoacyl synthase-acyl transferase [KS6][AT6] didomain, DEBS ACP6, and the ketoreductase domain from tylactone synthase module 1 (TYLS KR1) generated in situ anti-2a-ACP that underwent DH4-catalyzed syn dehydration to give 3-ACP. DH4 did not dehydrate syn-(2S,3R)-2b-ACP, syn-(2R,3S)-2c-ACP, or anti-(2S,3S)-2d-ACP generated in situ by DEBS KR1, DEBS KR6, or the rifamycin synthase KR7 (RIFS KR7), respectively. Similarly, incubation of a mixture of (2S,3R)-2-methyl-3-hydroxypentanoyl-N-acetylcysteamine thioester (2b-SNAC), methylmalonyl-CoA, and NADPH with DEBS [KS6][AT6], DEBS ACP6, and TYLS KR1 gave anti-(2R,3R)-6-ACP that underwent syn dehydration catalyzed by DEBS DH4 to give (4R,5R)-(E)-2,4-dimethyl-5-hydroxy-hept-2-enoyl-ACP (7-ACP). The structure and stereochemistry of 7 were established by GC-MS and LC-MS comparison of the derived methyl ester 7-Me to a synthetic sample of 7-Me.     

Separation of Leucas aspera,a medicinal plant of Bangladesh,guided by prostaglandin inhibitory and antioxidant activities

According to the traditional usage of the plant for antiinflammation and analgesia, Leucas aspera was tested for its prostaglandin (PG) inhibitory and antioxidant activities. The extract showed both activities, i.e., inhibition at 3 x 10(-4) g/ml against PGE(1)- and PGE(2)-induced contractions in guinea pig ileum and a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities in these dual assay methods provided eight lignans and four flavonoids, LA-1- -12, among which LA-1- -7 and LA-10- -12 were identified as nectandrin B, meso-dihydroguaiaretic acid, macelignan, acacetin, apigenin 7-O-[6"-O-(p-coumaroyl)-beta-D-glucoside], chrysoeriol, apigenin, erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol, myristargenol B, and machilin C, respectively. LA-8 was determined to be (-)-chicanine, the new antipode of the (+) compound, by spectroscopic methods including CD and ORD. Chiral-HPLC analysis of LA-9 showed that it was a mixture of two enantiomers, (7R, 8R)- and (7S, 8S)-licarin A. All of these components were first isolated from L. aspera. PG inhibition was observed in LA-1, LA-2, and LA-5, and antioxidant activity in LA-1- -3 and LA-8- -12.     

Enantioselective Hydrogenation over Chiral Cobalt Complexes with (+)-(1S,2S,5R)-Neomenthyldiphenylphosphine and (-)-(R,R)-2,2-Dimethyl-4,5-bis(diphenylphosphinomethyl)-1,3-dioxolane

The optical yield in enantioselective hydrogenation of methyl -acetamidocinnamate over mono- and diphosphine cobalt(II) complexes CoX₂L₂ [where X = Cl or CF₃SO₃, L = (+)-(1S,2S,5R)-neomenthyl-diphenylphosphine or L2' = (-)-(R,R)-2,2-dimethyl-4,5-bis(diphenylphosphinomethyl)-1,3-dioxolane], which are generated in situ, in the presence of sodium tetrahydridoborate increases with rise in the phosphine-to-metal ratio and hydrogen pressure. The maximal optical yields of (+)-(S)-N-acetylphenylalanine methyl ester attain 40% (CoX₂L₂) and 42% (CoX₂L₂').     

Electronic structure of nitric oxide adducts of bis(diaryl-1,2-dithiolene)iron compounds: four-membered electron-transfer series [Fe(NO)(L)2]z (z = 1+, 0, 1-, 2-)

Four members of the electron-transfer series [Fe(NO)(S(2)C(2)R(2))2]z (z = 1+, 0, 1-, 2-) have been isolated as solid materials (R = p-tolyl): [1a](BF4), [1a]0, [Co(Cp)2][1a], and [Co(Cp)2]2[1a]. In addition, complexes [2a]0 (R = 4,4-diphenyl), [3a]0 (R = p-methoxyphenyl), [Et(4)N][4a] (R = phenyl), and [PPh(4)][5a] (R = -CN) have been synthesized and the members of each of their electron-transfer series electrochemically generated in CH(2)Cl(2) solution. All species have been characterized electro- and magnetochemically. Their electronic, M?ssbauer, and electron paramagnetic resonance spectra as well as their infrared spectra have been recorded in order to elucidate the electronic structure of each member of the electron-transfer series. It is shown that the monocationic, neutral, and monoanionic species possess an {FeNO}6 (S = 0) moiety where the redox chemistry is sulfur ligand-based, (L)2-(L*)1-: [Fe(NO)(L*)2]+ (S = 0), [Fe(NO)(L*)(L)]0 <--> [Fe(NO)(L)(L*)]0 (S = 1/2), [Fe(NO)(L)2]- (S = 0). Further one-electron reduction generates a dianion with an {FeNO}7 (S = 1/2) unit and two fully reduced, diamagnetic dianions L2-: [Fe(NO)(L)2]2- (S = 1/2).     

Synthesis of the enantiomers of (3Z,9Z)-cis-6,7-epoxy-3,9-octadecadiene,one of the major components of the sex pheromone of Ectropis oblique Prout

Both enantiomers of (3Z,9Z)-cis-6,7-epoxy-3,9-octadecadiene, one of which is the major component of the sex pheromone of Ectropis oblique Prout, were synthesized in 23% overall yield for the (?)-(6S,7R)-enantiomer and 18% yield for the (+)-(6R,7S)-isomer. This protocol uses a sequential regioselective ring-opening strategy and provides a convenient and reliable access to other structurally related insect sex pheromones. Preliminary biological studies revealed that (?)-(6S,7R)-2a was roughly as active as the natural pheromone, while racemic (±)-2 was less bioactive and (+)-2b was much less bioactive.