Dienoic Esters Research Articles

ChemInform Abstract: Palladium‐Catalyzed Double‐Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

Palladium-Catalyzed Double-Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

New fatty acids from the Red Sea sponge Mycale euplectellioides

Chemical investigation of the Red Sea sponge Mycale euplectellioides afforded two new compounds; hexacosa-(6Z,10Z)-dienoic acid methyl ester (1) and hexacosa-(6Z,10Z)-dienoic acid (2), along with two known compounds: icosa-(8Z,11Z)-dienoic acid methyl ester (3) and β-sitosterol (4). The structures were elucidated by the interpretation of their spectral data. The total methanol extract (TME) of the sponge exhibited potent antimicrobial activity against the different strains at a concentration of 100 mg/mL. All tested fractions did not exhibit any activity against Serratia marcescens and tested fungal strains. The TME and different fractions displayed anti-inflammatory and antipyretic activities at doses of 100 and 200 mg/kg compared with indomethacin (8 mg). The TME exhibited a remarkable hepato-protective effect in CCl4-induced liver damage compared with silymarin. Furthermore, compounds 1 and 2 displayed weak activity against A549 non-small cell lung cancer, the U373 glioblastoma and the PC-3 prostate cancer cell lines.

Highly selective synthesis of conjugated dienoic and trienoic esters via alkyne elementometalation–Pd-catalyzed cross-coupling

All four stereoisomers (7-10) of ethyl undeca-2,4-dienoate were prepared in ≥ 98% isomeric purity by Pd-catalyzed alkenylation (Negishi coupling) using ethyl (E)- and (Z)-β-bromoacrylates. Although the stereoisomeric purity of the 2Z,4E-isomer (8) prepared by Suzuki coupling using conventional alkoxide and carbonate bases was ≤ 95%, as reported earlier, the use of CsF or (n)Bu(4)NF as a promoter base has now been found to give all of 7-10 in ≥ 98% selectivity. Other widely known methods reveal considerable limitations. Heck alkenylation was satisfactory for the syntheses of the 2E,4E and 2E,4Z isomers of ≥ 98% purity, but the purity of the 2Z,4E isomer was ≤ 95%. Mutually complementary Horner-Wadsworth-Emmons and Still-Gennari (SG) olefinations are also of considerably limited scopes. Neither 2E,4Z nor 2Z,4Z isomer is readily prepared in ≥ 90% selectivity. In addition to (2Z,4E)-dienoic esters, some (2Z,4E,6E)- and (2Z,4E,6Z)-trienoic esters have been prepared in ≥ 98% selectivity by a newly devised Pd-catalyzed alkenylation-SG olefination tandem process. As models for conjugated higher oligoenoic esters, all eight stereoisomers for ethyl trideca-2,4,6-trienoate (23-30) have been prepared in ≥ 98% overall selectivity.

Total synthesis of decarestrictine I and botryolide B via RCM protocol

A convergent stereoselective total synthesis of decarestrictine I (1) and botryolide B (1a) invoking a common synthetic strategy is reported. The key steps are: ring-closing metathesis of epoxy dienoic esters obtained through the Yamaguchi esterification of their respective intermediates to furnish the respective Z-macrocycles (2 and 2a) which were further extrapolated to their respective targets.

Synthesis and selective carbocupration reaction of fluorine-containing enynic esters, enynylphosphine oxides, and enynylphosphates

Some new fluorine-containing enynic esters, enynylphosphine oxides, and enynylphosphates were synthesized stereoselectively in good yields by the dehydrohalogenation reaction of fluoroalkylated 3-iodoacrylates, 2-iodovinylphosphonates, and 2-iodovinylphosphine oxides under basic conditions. These fluorine-containing enynic compounds could undergo carbocupration reaction with organocopper reagents and the vinylcopper intermediates formed in situ could further react with some electrophiles such as allyl bromide, phenylselenyl bromide, and iodine to give the corresponding polysubstituted fluorine-containing dienoic esters, phosphates, and phosphine oxides with high regio- and stereoselectivity.

Protecting group directed ring-closing metathesis (RCM): the first total synthesis of an anti-malarial nonenolide

The first synthesis of a newly found naturally occurring anti-malarial nonenolide is described. A pivotal step in the synthesis is the ring-closing metathesis of a dienoic ester prepared by coupling an acid and alcohol that were stereoselectively synthesized from ( S)-α-hydroxy-γ-butyrolactone and 1,2- O-isopropylidene d-glyceraldehyde, respectively.

A Stereoselective Suzuki Cross-Coupling Strategy for the Synthesis of Ethyl-Substituted Conjugated Dienoic Esters and Conjugated Dienones

A stereoselective approach towards ethyl-substituted conjugated dienoic esters and dienones utilising a Suzuki cross-coupling reaction has been achieved. In addition, a method for their conversion into the corresponding ethyl ketones is presented.

Sugar‐Modified Conjugated Diene Analogues of Adenosine and Uridine: Synthesis, Interaction with S‐Adenosyl‐L‐homocysteine Hydrolase, and Antiviral and Cytostatic Effects.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mixed peroxides from the chloroperoxidase-catalyzed oxidation of conjugated dienoic esters with a trisubstituted terminal double bond

The chloroperoxidase (CPO)-catalyzed oxidations of conjugated dienoic esters with a trisubstituted terminal double bond were studied by using tert-butyl hydroperoxide as the terminal oxidant. Most of the substrates gave disubstituted mixed peroxides as the major products.

Sugar-modified conjugated diene analogues of adenosine and uridine: synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects.

Moffatt oxidation of 2',3'-O-isopropylideneuridine (1a) and treatment of the crude 5'-aldehyde with formylmethylene-stabilized Wittig reagent gave the vinylogously extended 7'-aldehyde2a. Condensation of 2a with ethoxycarbonyl- or dibromomethylene phosphorane reagents gave the conjugated dienes 6a and 4a, respectively. Deacetonization gave diene ester 7a [5'(E),7'(E); with s-trans conformation] and dibromodiene 5a [5'(E)], respectively. Analogously, 2',3'-O-isopropylideneadenosine (1b) was Wittig-extended into the conjugated dibromodiene 5b [5'(E)] and dienoic ester 7b [5'(E),7'(E)]. Furthermore, palladium-catalyzed coupling of the vinyl 6'(E)-stannanes 14 with (E) and (Z) ethyl 3-iodoacrylate gave stereodefined access to dienoic esters 7 (E,E) and 16 (E,Z). Incubation of AdoHcy hydrolase with 100 microM of 5b resulted in partial inhibition of the enzyme without any apparent change in the enzyme's nicotinamide adenine dinucleoside (NAD(+)) content. In contrast, 7b and 16b produced time- and concentration-dependent inactivation of S-adenosyl-L-homocysteine (AdoHcy) hydrolase producing significant decreases in the enzyme's NAD(+) content. However, 7b and 16b upon incubation with AdoHcy hydrolase were not metabolized suggesting that these compounds are type I mechanism-based inhibitors. No specific antiviral activity was noted for 5a,b, 7a,b, and 16a,b against any of the viruses tested; dibromodiene 5b proved cytotoxic at a concentration > or =6.7 microM and cytostatic at > or =11 microM, while dienoic esters 16a,b showed activity against both varicella-zoster virus (at 10 microM, 16a) and cytomegalovirus (at 10 microM, 16a; 18 microM, 16b).

Stereopure 1,3-butadiene-2-carboxylates and their conversion into non-racemic α-alkylidenebutyrolactone natural products by asymmetric dihydroxylation

Dienoic esters 1 with the four possible permutations of the CC configurations were prepared in two steps via non-stereoselective aldol additions followed by stereospecific β-eliminations. Sharpless dihydroxylations of these esters yielded natural and unnatural α-alkylidene-β-hydroxybutyrolactones 2 . Among these were synthetic dihydromahubanolide B ( cis, Z- 2a ), isodihydromahubanolide B ( cis, E- 2a ) and, for the first time, litsenolide D 1 ( ent- trans, Z- 2b ) and the enantiomer trans, E- 2b of litsenolide D 2. Competitively, dihydroxyesters 10 were formed.

Synthesis of 3(Z)-dodecen-12-olide—an aggregation pheromone of the flat grain beetleCryptolestes pusillus (Coleoptera:Cucujidae)

3(Z)-Dodecen-12-olide, an aggregation pheromone of the flat grain beetle, was obtained using 1,4-cis-hydrogenation of ethyl 12-hydroxydodeca-2,4-dienoate as a key step. The dienoic ester was synthesized from 10-hydroxydec-2-enal, which, in turn, was prepa

Claisen rearrangement of γ-hydroxyvinyl sulfones via ketene acetal derivatives. A new entry to functionalized (2E,4E)-alkadienoic esters

In situ prepared ketene acetals of γ-hydroxyvinyl sulfones undergo a Claisen rearrangement affording 3-phenylsulfonyl esters. These compounds are converted to (2E,4E)-dienoic esters by a base-assisted elimination of benzenesulfinic acid.

A short synthesis of conjugated unsaturated alcohols

Isomerization of acetylenic pentafluorophenyl esters in the presence of phosphines gives rise to activated dienoic esters, which can be reduced directly in a simple one pot procedure to the corresponding conjugated unsaturated alcohols 6–10. The higher reactivity of the pentafluorophenyl esters in comparison to alkyl esters allows their selective isomerization.

Reaction of heterocyclic allyl sulphides with ethyl diazoacetate: a simple method for the synthesis of conjugated dienoic esters

Heterocyclic allyl sulphides 1–6 react with an excess of ethyl diazoacetate in the presence of copper(I)exafluorophosphate acetonitrile complex in dichloromethane under mild conditions to give, through the formation of homoallylic sulphides intermediates, conjugated dienoic esters in high yields.

A formal synthesis of (−)-pumiliotoxin C

Abstract An asymmetric synthesis of an advanced intermediate in the synthesis of natural (−)-pumiliotoxin C has been achieved in six steps and in 61 % overall yield employing as the key step a highly diasteroeselective lithium amide 1,4-conjugate addition to a dienoic ester derived from ( R )-(+)-pulegone.

A novel deoxygenation–isomerization reaction of 4-hydroxy-2-ynoic esters and γ-hydroxy-α,β-ynones

(2E, 4E)-Dienoic esters and (E,E)-α,β:γ,δ-dienones have been stereoselectively synthesized from 4-hydroxy-2-ynoic esters and γ-hydroxy-α,β-ynones by their reactions with triphenylphosphine under mild conditions.

Carbenoid entry into trifluoromethylated molecules: preparation of functionalized CF 3-containing γ, δ -unsaturated carboxylic esters by rhodium-catalyzed reaction of ethyl 3,3,3-trifluoro-2-diazo-propionate with allylic sulfides and their further facile conversion to trifluoromethylated conjugated dienoic esters

The [2,3]-sigmatropic rearrangement of sulfonium ylides derived from rhodium-catalyzed decomposition of ethyl 3,3,3-trifluoro-2-diazopropionate in the presence of allylic sulfides affords a variety of functionalized CF 3-containing γ , δ-unsaturated carboxylic esters which have been further converted to synthetically useful trifluoromethylated dienoic esters via the dehydrosulfenylation sequence. For the synthetic application, a novel fluorinated retinoid was synthesized.

ChemInform Abstract: Stereoselective Isomerization of Acetylenic Derivatives as a New Methodology in Organic Synthesis

The transition metal catalyzed isdmerization reac- tions of acetylenic derivatives were studied. (E,E)-Conju- gated dienones, dienoic esters and dienoic amides were syn- thesized from corresponding a,b-ynones, 2-ynoic esters and 2-ynoic amides, respectively. 2-Ynols were first isomerized to the corresponding 2-enones or 2-enals. The reactions can be accomplished simply, in high yield, and stereoselectively. It is proposed that allenic compounds are initially formed as the main intermediates and then isomerized further to the products. A convenient and potential useful methodology is provided for the preparation of important intermediates in the synthesis of natural products.