Phaseolinic Acid Research Articles

Tuber pathogenicity of Macrophomina phaseolina strain 3a isolated from rotten cassava tuber from farm lands in Osogbo, Osun State, Nigeria, its virulence genes and ADMET properties.

Macrophomina phaseolina is a pathogen that causes an opportunistic disease that spreads by soil and seeds and affects more than 500 different plant species, like fruits, trees, and row crops. Mycotoxins, such as phaseolinic acid, and phaseolinone, are produced by M. phaseolina isolates in previous investigations; however, the production of these mycotoxins seems to vary depending on the host and the region. In this study, Macrophomina phaseolina strain 3A was isolated from rotten cassava tuber and identified using the analysis of the sequences of the internal transcribed spacer region. The isolate was inoculated on a fresh healthy cassava tuber at 25°C and tuber-rotting potential was monitored for 4 weeks. Virulence genes MPH_06603, MPH_06955, and MPH_01521 were determined with designed primers, and secondary metabolites were characterized by FTIR and GCMS. The rotten tuber effect was observed from the 2nd week of the experiment with severe tuber rot and weight reduction. The PCR showed the presence of MPH_06603 virulence gene. The GCMS showed N-Methylpivalamide (115.0m/z), Butane, 1,4-dimethoxy- (119.0m/z), and 5-Hydroxymethylfurfural (126.0m/z) were the predominant metabolites produced by the pathogen. The compounds in the metabolites inhibit CYP3A4 enzymes, cause eye irritation, and Human Ether-a-go-go-related gene inhibition. This study revealed that M. phaseolina was responsible for the cassava tuber rot which leads to a lower yield of farm produce. The metabolites produced are toxic and unsafe for human consumption. It is suggested that farmers should destroy any cassava affected by this pathogen to prevent its toxic effects on humans and animals.

Nickel Carbene-Mediated One-Carbon Homologative γ-Butyrolactonization.

In this report, we present a highly efficient approach for the synthesis of β,γ-disubstituted γ-butyrolactone motifs. This newly developed strategy is based on the combination of a diastereoselective aldol and a nickel carbene-mediated γ-butyrolactonization and uses an effective intramolecular ring closure to rapidly access a range of functionalized chiral γ-butyrolactones. This single-step approach was applied to produce straightforward asymmetric syntheses of (-)-talaumidin methyl ether, (+)-veraguensin, and (+)-dubiusamine A and a formal synthesis of (+)-phaseolinic acid as one of the shortest syntheses disclosed to date.

Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species

AbstractWe report the diastereo‐ and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes in situ to α,β‐unsaturated diesters. In the presence of a chiral bisphosphine‐ligated CuH catalyst, the conjugate addition provides a direct access to enantioenriched alkylboron compounds containing two contiguous carbon stereogenic centers in good yield with high diastereo‐ and enantioselectivity (up to >98:2 dr, >99:1 er) by assembling readily available starting alkenyl reagents in a single operation without using preformed organometallic reagents or chiral auxiliaries. The resulting products were used in various organic transformations. The utility of the synthetic approach was highlighted by the synthesis of (−)‐phaseolinic acid.

Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species.

We report the diastereo- and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes in situ to α,β-unsaturated diesters. In the presence of a chiral bisphosphine-ligated CuH catalyst, the conjugate addition provides a direct access to enantioenriched alkylboron compounds containing two contiguous carbon stereogenic centers in good yield with high diastereo- and enantioselectivity (up to >98:2 dr, >99:1 er) by assembling readily available starting alkenyl reagents in a single operation without using preformed organometallic reagents or chiral auxiliaries. The resulting products were used in various organic transformations. The utility of the synthetic approach was highlighted by the synthesis of (-)-phaseolinic acid.

A protecting-group-free synthesis of (+)-nephrosteranic, (+)-protolichesterinic, (+)-nephrosterinic, (+)-phaseolinic, (+)-rocellaric acids and (+)-methylenolactocin.

A collective synthesis of a γ-butyrolactone class of paraconic acids such as (+)-methylenolactocin, (+)-phaseolinic acid, (+)-nephrosteranic acid, (+)-nephrosterinic acid, (+)-rocellaric acid and (+)-protolichesterinic acid is described. The strategy adopted is protecting-group-free based on efficient Pd-catalyzed Suzuki-Miyaura coupling and Ru-catalyzed Sharpless oxidation to construct the core β-CO2H-γ-butyrolactone unit to accomplish the synthesis of various paraconic acids.

A concise synthesis of paraconic acids: (−)-methylenolactocin and (−)-phaseolinic acid

A concise synthesis of (−)-methylenolactocin and (−)-phaseolinic acid, the common members of the paraconic acids, is described. The synthesis is based on regioselective asymmetric dihydroxylation and the orthoester Johnson–Claisen rearrangement of allyl alcohol with a vicinal diol functionality as the key steps. The synthesis was completed in 10 steps with overall yields of 4.1% for (−)-methylenolactocin and 4.3% for (−)-phaseolinic acid.

Formation of γ-Lactones through CAN-Mediated Oxidative Cleavage of Hemiketals

The generation of substituted gamma-lactones can be accomplished through application of a tandem chain extension-aldol reaction, followed by CAN-mediated oxidative cleavage of the aldol product. The oxidative cleavage requires the intermediacy of a hemiketal and the presence of an alpha-heteroatom. Formation of the gamma-lactone through the oxidative cleavage is used to assign stereochemistry of the aldol reaction and as the final step in a short synthesis of members of the phaseolinic acid family of natural products.

General Enantioselective Synthesis of Butyrolactone Natural Products via Ruthenium‐SYNPHOS®‐Catalyzed Hydrogenation Reactions

AbstractEnantioselective syntheses of several paraconic acids have been achieved using catalyzed asymmetric hydrogenation of β‐keto esters with SYNPHOS® as a ligand. This strategy allowed the short synthesis of biologically active (−)‐methylenolactocin 1, (−)‐protolichesterinic acid 2, (−)‐phaseolinic acid 3 and (+)‐roccellaric acid 4.

Synthesis of (-)-Phaseolinic Acid

The synthesis of (-)-phaseolinic acid exemplifies a procedure for the Cu(I)-catalyzed asymmetric 1,4-addition of Grignard reagents to α,β-unsaturated thioesters followed by aldol reaction of the resultant magnesium enolates with aldehydes to give syn,syn-stereotriads with excellent diastereo- and enantioselectivity. The method is a rare example of the asymmetric conjugate addition of an organometallic reagent to an acyclic α,β-unsaturated carbonyl derivative.

Synthesis of substituted butenolides by the ring closing metathesis of two electron deficient olefins: a general route to the natural products of paraconic acids class

A variety of allyl acrylates possessing electron-withdrawing groups undergo RCM using the second generation Grubbs’ catalyst in the presence of a Lewis acid resulting in diverse butenolides in high isolated yields. This methodology provides a general route to the natural products of paraconic acids class, exemplified by a total synthesis of (±)-phaseolinic acid.

Catalytic Asymmetric Synthesis of Acyclic Arrays by Tandem 1,4-Addition-Aldol Reactions

Herein, we report efficient acyclic stereocontrol in tandem 1,4-addition-aldol reactions triggered by catalytic asymmetric organometallic addition. Grignard reagents add to alpha,beta-unsaturated thioesters in a 1,4-fashion and the resulting magnesium enolates are trapped with aromatic or aliphatic aldehydes. The process provides a range of tandem products bearing three contiguous stereocenters with excellent control of relative and absolute stereochemistry. The various diastereomeric products have been fully characterized using single-crystal X-ray analysis and the origins of stereocontrol in this tandem protocol are discussed. The versatility and efficiency of this methodology are demonstrated in the first catalytic asymmetric synthesis of (-)-phaseolinic acid with 54% overall yield via a short and concise route.

A Straightforward Synthesis of (‐)‐Phaseolinic Acid.

A concise approach to (-)-phaseolinic acid starting from commercially available (S)-oct-1-yn-3-ol is disclosed. The key steps are a ring-closing metathesis reaction to prepare a C(2)-symmetrical allylic diol and its desymmetrization to a gamma-butyrolactone by using an Ireland-Claisen rearrangement. The 2S,3S,4S configuration of the levogyre natural product has been confirmed.

A Straightforward Synthesis of (−)-Phaseolinic Acid

A concise approach to (-)-phaseolinic acid starting from commercially available (S)-oct-1-yn-3-ol is disclosed. The key steps are a ring-closing metathesis reaction to prepare a C(2)-symmetrical allylic diol and its desymmetrization to a gamma-butyrolactone by using an Ireland-Claisen rearrangement. The 2S,3S,4S configuration of the levogyre natural product has been confirmed.

Synthesis of (.+‐.)‐Nephromopsinic, (‐)‐Phaseolinic, and (‐)‐Dihydropertusaric Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of (±)-Nephromopsinic, (−)-Phaseolinic, and (−)-Dihydropertusaric Acids

The formal syntheses of (±)-nephromopsinic acid, (−)-phaseolinic acid, and the first total synthesis of (−)-dihydropertusaric acid from (±)- and (−)-7-oxabicyclo[2.2.1]hept-5-en-2-one are described. These syntheses take advantage of a previously reported radical rearrangement (1,2-acyl migration). A remarkable iodide-mediated cleavage of a bicyclic system, followed by the introduction of the γ-chains via a mixed Kolbe electrolysis, are the key steps of these syntheses. This approach is general and could be applied for the preparation of all kinds of paraconic acids with excellent control of the stereochemistry.

Vicinal Dianion of Triethyl Ethanetricarboxylate: Syntheses of (±)-Lichesterinic Acid, (±)-Phaseolinic Acid, (±)-Nephromopsinic Acid, (±)-Rocellaric Acid, and (±)-Dihydroprotolichesterinic Acid

The vicinal dianion 2 derived from triethyl ethanetricarboxylate reacted regioselectively with aldehydes and ketones at C(β) to provide paraconic acid derivatives 5a–f in moderate to high yields as mixtures of diastereoisomers. The paraconic acid derivatives 5e and 5f were utilized as the starting materials for the syntheses of (±)-lichesterinic acid (12), (±)-phaseolinic acid (13), (±)-nephromopsinic acid (14), (±)-rocellaric acid (15), and (±)-dihydroprotolichesterinic acid (16).

A concise synthesis of (±)-methylenolactocin and the formal synthesis of (±)-phaseolinic acid

(±)-Methylenolactocin was prepared in five steps involving an indium-mediated allylation reaction as the key step.

ChemInform Abstract: Synthesis of (+)‐ and (‐)‐Phaseolinic Acid by Combination of Enzymatic Hydrolysis and Chemical Transformations with Revision of the Absolute Configuration of the Natural Product.

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Synthesis of (+)- and (−)-Phaseolinic Acid by Combination of Enzymatic Hydrolysis and Chemical Transformations with Revision of the Absolute Configuration of the Natural Product

Synthesis of (+)- and (−)-Phaseolinic Acid by Combination of Enzymatic Hydrolysis and Chemical Transformations with Revision of the Absolute Configuration of the Natural Product

Asymmetric resolution of diastereomeric 4-ethoxycarbonyl-5-pentyl-γ-butyrolactones by crude PLE-mediated hydrolysis

Chemical reduction of diethyl 1-oxo-hexylsuccinate resulted in the formation of the corresponding cis and trans disubstituted γ-butyrolactones. Both racemic diastereomers were resolved by means of lipolytic enzymes leading to the precursors of interesting natural products such as (−)-methylenolactocin and (−)-phaseolinic acid.