Concise Synthesis of (8Z,11Z,14Z)-8,11,14-Heptadecatrienal, (7Z,10Z,13Z)-7,10,13-Hexadecatrienal,and (8Z,11Z)-8,11-Heptadecadienal,Components of the Essential Oil of Marine Green Alga Ulva pertusa

The long-chain aldehydes, (8Z,11Z,14Z)-8,11,14-heptadecatrienal, (7Z,10Z,13Z)-7,10,13-hexadecatrienal, and (8Z,11Z)-8,11-heptadecadienal, were concisely synthesized by using Grignard coupling, catalytic hydrogenation with the Lindlar catalyst, and oxidation with Dess–Martin periodinane as the key steps. Particularly, (8Z,11Z,14Z)-8,11,14-heptadecatrienal and (7Z,10Z,13Z)-7,10,13-hexadecatrienal both possessed a seaweed-like odor.     

Synthesis and Evaluation of Novel Oligodeoxynucleotides Containing 3′-C-(3-Benzoyloxypropyl)thymidine and Bicyclo Nucleoside Derivatives

Abstract

The stereoselective synthesis of 3′-C-Allyluridine derivative 2 has been accomplished. This nucleoside was used as a key synthon for the synthesis of oligodeoxynucleotides containing 3′-C-(3-benzoyloxypropyl)thymidine (X) or bicyclo nucleoside (Y+Z) monomers. Preliminary thermal experiments are reported.     

A Convenient Synthesis of a Mixture of (Z,Z)-3,13-Octadecadienyl Acetate and Its (E,Z)-Isomer,the Attractant for the Cherrytree Borer

A 1:1 mixture of (Z, Z)-3,13-octadecadien-1-ol and its (E, Z)-isomer was synthesized by a Wittig reaction whose stereoselectivity was adjusted to give the products in the required ratio. The corresponding acetate mixture is useful as the attractant for Synanthedon hector.     

(10E,12Z,15Z)-9-Hydroxy-10,12,15-octadecatrienoic Acid Methyl Ester as an Anti-inflammatory Compound from Ehretia dicksonii

The methanol extract of Ehretia dicksonii provided (10E,12Z,15Z)-9-hydroxy-10,12,15-octadecatrienoic acid methyl ester (1) which was isolated as an anti-inflammatory compound. Compound 1 suppressed 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced inflammation on mouse ears at a dose of 500 μg (the inhibitory effect (IE) was 43%). Linolenic acid methyl ester did not inhibit this inflammation at the same dose. However, the related compounds of 1, (9Z,11E)-13-hydroxy-9,11-octadecadienoic acid (5) and (9Z,11E)- 13-oxo-9,11-octadecadienoic acid (6), showed potent activity (IE_{500 μg} of 63% and 79%, respectively). Compounds 1, 4 ((9Z,12Z,14E)-16-hydroxy-9,12,14-octadecatrienoic acid), 5 and 6 also showed inhibitory activity toward soybean lipoxygenase at a concentration of 10 μg/ml.     

Synthesis of (3E, 5Z)-3,5-Dodecadienylacetate,the Sex Pheromone of Phtheochroa cranaodes (Lepidoptera: Tortricidae)

(3E, 5Z)-3,5-Dodecadienyl acetate, the female sex pheromone of Phtheochroa cranaodes, was regio and stereo-selectively synthesized from 1-octyne and (E)-4-bromo-3-buten-1-ol by using Pd(PPh₃)₄, CuI and piperidine to afford the enyne (5). Further elaboration afforded the target pheromone. The synthetic pheromone was identified with the natural product by its MS and IR, data GLC retention time and biological activity.     

Responses of male winter moths (Operophtera brumata) to their sex attactant (3Z,6Z,9Z)-1,3,6,9 nonadecatetraene and to some structural analogues

Conclusion (3Z,6Z,9Z)-1,3,6,9-nonadecatetraene, the synthetic sex pheromone of the female of O. brumata is highly active in attracting males of this species in the field (Germany and Switzerland). No analogous compounds possessing attractivity to O. brumata males have been found up to now, nor did they show any inhibitory effects to the same species.Therefore (3Z,6Z,9Z)-1,3,6,9-nonadecatetraene (I) can be recommended as a good attractant in the prognosis or monitoring of this lepidopteran pest.     

Stereoselective Synthesis of a Promising Flower-Inducing KODA Analog, (9R,12S,13R,15Z)-9-Hydroxy-12,13-methylene-10-oxooctadec-15-enoic Acid

Stereoselective synthesis of a promising flower-inducing 9,10-ketol octadecadienoic acid (KODA) analog, (9R,12S,13R,15Z)-9-hydroxy-12,13-methylene-10-oxooctadec-15-enoic acid, was designed to obtain the desired stereoisomer via coupling between chiral sulfone and aldehyde segments. A known chiral cyclopropane derivative was converted to the sulfone segment via carbon-chain elongation and sulfonylation. Dec-9-en-1-ol was converted to the aldehyde segment, whose C-9 configuration was introduced by Sharpless asymmetric dihydroxylation. Coupling of the both segments and subsequent assembly gave the desired (9R,12S,13R,15Z)-analog. The (9S,12S,13R,15Z)-analog was also synthesized by using the enatiomeric aldehyde segment. This strategy made it possible to synthesize the remaining stereoisomeric analogs.     

(Z)-1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane: The synthesis and enantiomeric separation of an antitumor agent

(Z)-1,1-Dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane ( 5 ), a potential antitumor agent designed to treat breast cancer, was prepared in three steps. A stereospecific palladium-catalyzed cross coupling reaction which provided the intermediate (Z)-triaryl alkene 4 was a crucial step in the synthesis. Makosza phase transfer reaction on 4 gave the enantiomeric (Z)-dichlorocyclopropane derivatives 5 which were resolved by semipreparative HPLC on a chiral stationary phase consisting of amylose tris-3,5-dimethylphenyl carbamate coated on silica gel. © 1994 Wiley-Liss, Inc.     

Simple Synthesis of Mite Pheromone β-Acaridial and Its Analogs in the Secretion of Caloglyphus polyphyllae (Acari: Acaridae)

A simple synthesis of β-acaridial [(E)-1], the active principle of the sex, alarm and aggregation pheromone among astigmatid mites, was achieved in 5 steps from 1,2,4-butanetriol 2 in a 19% overall yield. Its analog, β-acariolal 8, was also prepared in a 63% yield by oxidation of the intermediate, β-acaridiol [(E)-7], with pyridinium dichromate (PDC). This synthetic route also gave β-(Z)-acaridiol [(Z)-7] by using a Z-selective base in the Wittig reaction. (Z)-7 was oxidized to give a new monoterpene, β-(Z)-acaridial [(Z)-1], which was detected as a trace component in the secretion of Caloglyphus polyphyllae, together with 8.     

Syntheses of Alarm Pheromone Analogues of the Mold Mite,Tyrophagus putrescentiae,and Their Biological Activities

Against the mold mite, Tyrophagus putrescentiae, 3,7-dimethyl-(Z)-2-octenyl formate (II) is the most active compound as an alarm pheromone besides the natural pheromone, neryl formate (I), and this activity is equal to I (1-10 ppm). In order to elucidate the structural requisites for inducing alarm pheromone activity, a total of 16 analogues of I were prepared by modifying the structure of II. For preparation of 3-methyl- and 3-ethyl-(Z)-2-alkenyl formates, the Wittig reaction of ethoxy- or methoxy-carbonylmethylene triphenyl phosphorane with 2-alkanone or 3-alkanone was used. The reaction with 2-alkanone gave a mixture of (Z)-2-alkenoate (ca. 40%) and (E)-2-alkenoate (ca. 60%) in an average 60% yield. The reaction with 3-alkanone gave a mixture of (Z)-2-alkenoate (56%) and (E)-2-alkenonate (44%).

Alarm pheromone activities were demonstrated on 14 compounds of (Z)-2-alkenyl formates. The presence of the (Z)-allylic primary alcohol formate moiety in a molecule was clarified as the key to induce pheromone activity, and no necessity for an acyclic monoterpene carbon skeleton was demonstrated.     

Identification of the New Hydrocarbon (Z,Z)-1,6,9-Heptadecatriene as the Secretory Component of Caloglyphus polyphyllae (Astigmata: Acaridae)

A new heptadecatriene was isolated from the acarid mite, Caloglyphus polyphyllae, as the major characteristic component which could be used to identify the species chemo-taxonomically. Its structure was elucidated as 1,6,9-heptadecatriene by partial hydrogenation and a subsequent GC/MS analysis of the dimethyldisulfide derivative, together with evidence of the terminal vinyl group and Z-configuration of double bonds that was provided by GC-FT/IR and NMR. The triene was identified as (Z,Z)-1,6,9-heptadecatriene by its synthesis and is revealed to be a new compound as a natural product.     

Novel Synthesis of (Z)-3-Hexen-1-ol and cis-Jasmone

Both (Z)-3-hexen-1-ol and cis-jasmone were synthesised via 1,4-selective hydrogenation of conjugated dienes in the presence of arene Cr(CO)₃ or Cr(CO)₆ catalysts as the key step.     

Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol

Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol synthesis is high. Unlike desmosterol (1), neither of these isomers is a ligand to the liver x receptors and thus represents a novel biological deactivation mechanism avoiding cholesterol synthesis.     

Synthesis of 3Z, 6Z-Dienoic Acids

3Z,6Z-Dienoic acids (C₈-C₁₂ and C₁₈) were for the first time synthesized by coupling 2-acetylenic bromides and 2-(3′-butynyloxy)-tetrahydropyrane followed by stereoselective hydrogenation and oxidation.     

Ethynylglycine synthon from Garner’s aldehyde: a useful precursor for the synthesis of non-natural amino acids

Summary. The ethynylglycine synthon, namely (R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-ethynyl-oxazolidine, can be obtained through the synthetic elaboration of naturally occurring serine. This compound has been exploited as a helpful and versatile non-racemic building block to be used for the design and synthesis of biologically important compounds, mainly non-natural α-amino acids. Taking advantage of the terminal acetylene moiety several synthetic applications can be designed. Metalation followed by trapping with electrophiles or Cu/Pd catalysed coupling with aromatic halogenides are shown to deliver useful precursors of ethynylglycine derivatives. Additions of bimetallic reagents like stannyl- or silylcuprates are useful entries for the regio- and stereoselective functionalization of the lateral chain, aimed at the synthesis of modified vinylglycine precursors.An overview of our recent work in the field will be given, and the use of ethynylglycine synthon in the synthesis of non-racemic saturated and unsaturated non-natural amino acids will be briefly reviewed.     

(Z)-3-nonenol, (Z,Z)-3,6-nonadienol and (S,S)-(-)-epianastrephin: male produced pheromones of the Mexican fruit fly

(Z)-3-nonenol, (Z,Z)-3,6-nonadienol and (S,S)-(-)-epianastrephin proved active as male-produced pheromones which elicited behavioral responses from virgin female Mexican fruit flies (Anastrepha ludens) (Diptera: Tephritidae) in laboratory bioassays. All three chemicals elicited attraction and/or locomotor arrest when tested individually. When tested together, (Z)-3-nonenol inhibited the behavioral effect of (Z,Z)-3,6-nonadienol but either of the alcohols synergized the effect of (S,S)-(-)-epianastrephin. Quantities of the pheromones per male abdomen were: (Z)-3-nonenol-100 ng; (Z,Z)-3,6-nonadienol-40 ng; and total epianastrephin (R,R and S,S enantiomers)-700 ng. Relative to the quantities in abdominal extract, males released these chemicals during sexual display in a blend containing a higher proportion of the alcohols.

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Résumé Le (Z)-3-nonènol, le (Z,Z)-3,6-nonadiènol et le (S,S)-(-)-épianastréphine produits par les mâles de la mouche mexicaine du fruit (Anastrepha ludens) (Diptera: Tephritidae) ont attirés les femelles lors de tests conduits en laboratoire. Le pouvoir attractif du (Z)-3-nonènol est faible comparé à celui des deux autres phéromones. Evalués ensemble, le (Z)-3-nonènol inhibe l'attractivité du (Z,Z)-3,6-nonadiènol mais chacun des deux alcools synergise l'effet attractif de la (S,S)-(-)-épianastréphine. Les quantités recouvrées par mâle dans un extrait abdominal étaient respectivement de 100, 40 et 700 ng pour le (Z)-3-nonènol, le (Z,Z)-3,6-nonadiènol, et l'épianastréphine totale (R,R et S,S) énantiomères. Comparées à ces valeurs, le mélange élange émis par les mâles lors de leur cour sexuelle est plus riche in alcools. Le rapport (Z)-3-nonènol (Z,Z)-3,6-nonadiènol est cependant identique dans l'extrait abdominal et dans le mélange émis par les mâles.

     

Components of the female sex pheromone of the yellow stem borer, Scirpophaga incertulas

Ovipositor washings and volatiles from virgin female Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae) were analysed by gas chromatography (GC) linked to electroantennography (EAG). Two EAG responses were observed at retention times consistent with those of monounsaturated 16-carbon aldehydes and monounsaturated 16-carbon alcohols. Analysis of ovipositor washings on high-resolution, capillary GC columns showed peaks which cochromatographed with (Z)-11-hexadecenal, (Z)-9-hexadecenal, (Z)-11-hexadecen-1-ol and hexadecanal. EAG responses of male S. incertulas to synthetic hexadecenal isomers were greatest for the (Z)-11 and (Z)-11 isomers. Field tests in the Philippines showed that traps baited with a mixture of (Z)-11-hexadecenal and (Z)-9-hexadecenal in the naturally occurring 3:1 ratio caught significantly more male S. incertulas moths than those baited with a virgin female moth. Addition of (Z)-11-hexadecen-1-ol to this mixture reduced trap catches.

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Résumé Des produits provenant du lavage d l'ovipositeur et des substances volatiles de femelles vierges de S. incertulas Walker (Lep.: Pyralidae) ont été examinées en chromatographie en phase gazeuse (GC) avecélectroantennogramme simultané(EAG). Deux réponses EAG ont été enregistrées à des temps de rétention correspondant à ceux des aldéhydes monoinsaturés 16 carbones et des alcools monoinsaturés 16 carbones. L'analyse des produits provenant du lavage de l'ovipositeur en colonnes GC capillaires à haute résolution a donné des pics correspondant aux (Z)-11-hexadécenal, (Z)-9-hexadécenal, (Z)-11-hexadecen-1-ol et à l'hexadecanal. Les réponses EAG de mâles de S. incertulas aux isomères synthétiques d'hexadécenal étaient plus intenses pour les isomères (Z)-11 et (E)-11. Des essais en champ aux Philippines ont montré que les pièges contenant un mélange de (Z)-11-hexadécenal et de (Z)-9-hexadécenal dans le rapport natural 3/ 1 capturaient plus de mâles de S. incertulas que ceux contenant une femelle vierge. L'addition au mélange de (Z)-11-hexadecen-1-ol réduit les captures.

     

(Z)-8-dodecenyl acetate: the major component of the female sex pheromone of Cryptophlebia batrachopa, a Tortricid pest of macadamia in Malawi

Ovipositor washings from virgin female Cryptophlebia batrachopa (Meyrick) (Lepidoptera: Tortricidae) were analysed by gas chromatography (GC) linked to electroantennography (EAG) and by high-resolution GC. The major EAG-active component in ovipositor washings was shown to be (Z)-8-dodecenyl acetate with less than 0.5% of the E isomer. GC analysis of ovipositor washings from C. leucotreta confirmed the presence of approximately equal amounts of (Z)- and (E)-8-dodecenyl acetates (Persoons et al., 1977). When pure (Z)-8-dodecenyl acetate and mixtures containing up to 50% of the E isomer were tested in the field in Malawi where both Cryptophlebia species occurred, C. batrachopa male moths were caught only in traps baited with 10% or less of the E isomer and highest catches were recorded for the pure Z isomer. By contrast C. leucotretra males were caught predominantly by traps baited with more than 10% E isomer and no catches were recorded for the pure Z isomer. (Z)-8-dodecenyl acetate containing 1% of the E isomer was found to attract male moths of Opogona spp.

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Résumé Les produits recueillis par lavages de l'ovipositeur de Cryptophlebia batrachopa Meyr. (Lep. Tortricidae) ont été analysés par chromatographie gazeuse (GC) associée à l'électroantennographie (EAG) et la GC à haute résolution. Le principal constituant actif en EAG provenant des lavages s'est révélé être le (Z)-8-dodécényl acétate avec moins de 0,5% de l'isomère E. L'analyse GC de ces produits de lavage de C. leucotreta ont confirmé la présence d'à peu près les mêmes quantités de (Z) et (E)-8-dodécényl acétates (Persoons et al., 1977). Quand des essais sur le terrain ont été effectués au Malawi, où existent les deux espèces de Cryptophlebia, avec du (Z)-8-dodécényl acétate et des mélanges comprenant jusqu'à 50% de l'isomère E, des mâles de C. batrachopa ont seuls été capturés dans des pièges contenant 10% ou moins de l'isomère E; les captures les plus élevées ont été obtenues avec l'isomère Z pur. A l'opposé, surtout des mâles de C. leucotreta ont été capturés dans des pièges garnis avec plus de 10% d'isomère E, et aucune capture n'a été obtenue avec l'isomère Z pur. Des mâles d'Opogona spp. ont été attirés par du (Z)-8-dodécényl acétate contenant 1% de l'isomère E.

     

A Novel Convergent Synthesis of the Antiglaucoma PGF2α Analogue Bimatoprost

The 17‐phenyl PGF_2α analogue bimatoprost ( 10a ) is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma or ocular hypertension. A novel convergent synthesis of 13,14‐en‐15‐ol prostamideF_2α analogues was developed employing Julia–Lythgoe olefination of the structurally advanced phenylsulfone (+)‐(5Z)‐ 15 with an enantiomerically pure aldehyde ω‐chain synthon (–)‐(S)‐ 16a . Subsequent hydrolysis of protecting groups and final amidation of the diol 26a yielded bimatoprost ( 10a ). The main advantage of the current strategy is the preparation of high‐purity bimatoprost ( 10a ). The novel convergent strategy allows the synthesis of a whole series of 13,14‐en‐15‐ol prostamideF_2α analogues with the desired C‐15 asymmetric center configuration from a common and structurally advanced prostaglandin intermediate (+)‐(5Z)‐ 15 . The preparation and identification of two synthetic impurities, 15‐epi isomer ( 10b ) of bimatoprost and a new prostaglandin related amide (+)‐(5Z)‐ 18 , are also described. Chirality 25:170–179, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-H8]-analogues through a common synthetic route

Total synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-³H₈]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis.