Lycoperdic Acid Research Articles

Total synthesis of lycoperdic acid and stereoisomers (part 1): Double asymmetric hydrogenation of a racemic enamide

Design, synthesis, and double asymmetric hydrogenation of a racemic enamide are reported toward stereodivergent synthesis of lycoperdic acid and its isomers. The hydrogenation outcome (yield, ee) was used to identify matched and mismatched products, the information is important to clarify the reaction mechanism. It is also proposed that if the reaction mechanism is known, structure of the products would be identified without spectroscopic analyses from the matched/mismatched analysis.

Total synthesis of lycoperdic acid and stereoisomers (part 2): Completion of the synthesis and biological evaluation

Mushroom-derived glutamate natural product lycoperdic acid and its three stereoisomers were synthesized in 1.2–7.1% yield for total 11 steps from 2,2-dimethyl-1,3-dioxan-5-one. This paper describes the second half of these synthetic works via a suitably protected amino acid intermediate with stereochemically defined complete carbon chain each. The neuronal activities are also reported.

Synthesis of both enantiomers of lycoperdic acid, an unusual mushroom-derived amino acid

An efficient synthesis of both enantiomers of lycoperdic acid, a 4-hydroxyglutamic acid derivative from edible mushroom Lycoperdon perlatum, was achieved from a chiral aminoalcohol. The key steps were a stereoselective introduction of a C3 unit into a bicyclic ketone and oxidative cleavage of a cyclic vicinal diol into a dicarboxylic acid. This report provides the first synthesis of (-)-lycoperdic acid.

Catalytic Enantioselective Total Synthesis of (+)-Lycoperdic Acid.

A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama-Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.

Total synthesis of lycoperdic acid and its C4-epimer

Efficient stereodivergent syntheses of (+)-lycoperdic acid (LPA) and 4-epi-LPA have been achieved based on asymmetric hydrogenation (H2, Rh/(R,S)-MeBoPhoz) of racemic enamide as a key step.

3-Alkyl-1,2-cyclopentanediones by Negishi cross-coupling of a 3-bromo-1,2-cyclopentanedione silyl enol ether with alkylzinc reagents: an approach to 2-substituted carboxylic acid γ-lactones, homocitric and lycoperdic acids

Negishi cross-coupling of the silyl-protected 3-bromoenol of 1,2-cyclopentanedione with primary and secondary alkylzinc reagents using Pd-catalysts affords 3-alkyl substituted 1,2-cyclopentanediones in good yield. The method was applied to obtain 3-methylalkoxycarbonyl- and 3(2-Boc-aminoethyl)-alkoxycarbonyl-1,2-cyclopentanediones—homocitric and lycoperdic acid precursors. Homocitric and lycoperdic acids were synthesized using asymmetric oxidation with the Ti(OiPr)4/tartaric ester/tBuOOH complex in two steps from the obtained precursors.

Visible Light‐Mediated Synthesis of (Spiro)anellated Furans

AbstractVisible light‐mediated decarboxylation using N‐acyloxyphthalimides as the source for carbon‐centered radicals was applied for the synthesis of spirobutenolides. The utility of this approach is demonstrated with the formal synthesis of (S)‐(+)‐lycoperdic acid. Alternatively, 2,3‐anellated furans can be obtained in a one‐pot procedure via photocyclization following a regioselective semipinacol rearrangement.magnified image

ChemInform Abstract: Stereocontrolled Synthesis of (+)-Lycoperdic Acid Based on a Palladium Catalyzed Reaction Using a Serine-Derived Organozinc Reagent.

An efficient stereocontrolled synthesis of (+)-lycoperdic acid has been achieved based on palladium catalyzed cross-coupling reaction of (Z)-1-(tert-butyldimethylsiloxy)-3-iodo-6-(p-methoxybenzyl)oxy-2-hexene with the organozinc reagent, prepared from N-Boc-β-iodoalanine methyl ester.

機能性ニトロンを用いたアミノ酸型天然物の合成研究

(5R)- [and (5S)]-5,6-Dihydro-5-phenyl-2H-1,4-oxazin-2-one N-oxides were designed and synthesized as chiral (E)-geometry-fixed α-alkoxycarbonylnitrones that exist as equilibrating mixture of (E)- and (Z)-isomers. The cyclic nitrone reacted with olefins under mild conditions to afford the main cycloadducts via the least sterically demanding exo modes. The nitrone also reacted with an allyl alcohol in the presence of magnesium bromide from the less hindered face via exo-mode to afford exclusively cycloadduct as a single stereoisomer. These reactions were applied to the syntheses of carbocyclic polyoxin C, anti-β-substituted aspartic acid, clavalanine, monatin, lycoperdic acid, neodysiherbaine A, and maremycins A and D1.

ChemInform Abstract: Diastereoselective Synthesis of Glutamate‐Appended Oxolane Rings: Synthesis of (S)‐(+)‐Lycoperdic Acid (I).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Diastereoselective Synthesis of Glutamate-Appended Oxolane Rings: Synthesis of (S)-(+)-Lycoperdic Acid

The stereocontrolled synthesis of the glutamate-containing natural product (S)-(+)-lycoperdic acid is described. The key transformation in the synthetic route was an efficient diastereoselective annulation of an oxolane ring onto a pyroglutamate scaffold to construct either a gamma,gamma-disubstituted glutamate-appended tetrahydrofuran or a gamma-lactone. The reaction sequence also featured an improved method for the halogenation of pyroglutamate derivatives in high yield with enhanced stereoselection.

Stereoselective Syntheses of 4‐Hydroxy 4‐Substituted Glutamic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective Syntheses of 4-Hydroxy 4-Substituted Glutamic Acids

The 4-hydroxy 4-substituted glutamic acid moiety is a common substructure of biologically important natural products such as monatin [(2S,4S)-2], lycoperdic acid (3), and dysiherbaine (4). To develop methodology for syntheses of these natural products, cycloadditions of nitrone 5 with 2-substituted 2-propen-1-ols 6 and 2-substituted acrylates 8 were investigated. Reactions of nitrone 5 with alcohols 6 in the presence of MgBr2OEt2 gave cycloadducts 7 in a highly stereoselective manner, whereas noncatalyzed reactions of 5 with acrylates 8 afforded adducts 9. Using the former reaction, syntheses of monatin [(2S,4S)-2], monatin derivative 18, and lycoperdic acid (3) were accomplished. The C4-epimer of monatin [(2S,4R)-2)] was also synthesized by employing the latter cycloaddition.

Stereoselective synthesis of ( S)-(+)-lycoperdic acid through an endo selective hydroxylation of the chiral bicyclic lactam enolate with MoOPH

Efficient synthesis of ( S)-(+)-lycoperdic acid has been achieved by use of the stereoselective hydroxylation of the enolate derived from the bicyclic lactam 3 with the molybdenum oxidizing reagent, MoOPH (MoO 5·Py·HMPA, oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide)), as a key step.

Stereocontrolled synthesis of (+)-lycoperdic acid based on a palladium catalyzed reaction using a serine-derived organozinc reagent

An efficient stereocontrolled synthesis of (+)-lycoperdic acid has been achieved based on palladium catalyzed cross-coupling reaction of ( Z)-1-( tert-butyldimethylsiloxy)-3-iodo-6-( p-methoxybenzyl)oxy-2-hexene with the organozinc reagent, prepared from N-Boc-β-iodoalanine methyl ester.

Asymmetric Synthesis of Lycoperdic Acid.

Lycoperdic acid [(2S, 5'S)-2-amino-3-(5'-carboxy-2'-oxo-5'-tetrahydrofuranyl)propanoic acid], isolated from the mushroom Lycoperdon perlatum, was synthesized from trans-4-hydroxy-L-proline by a six-step route involving samarium diiodide (SmI2)-mediated formation of the spiro-γ-lactone and ruthenium tetroxide (RuO4) oxidation of the L-proline ring system to the L-pyroglutamic acid moiety. Lycoperdic acid (1) was found to undergo hydrolysis of the γ-lactone ring in 1 N hydrochloric acid at 23°C, giving an equilibrated mixture of 1 and the corresponding hydroxy acid.

First synthesis of lycoperdic acid

Lycoperdic acid, (2S,2′S)-2-amino-3-(2′-car☐y-5′-oxo-2′-tetrahydrofuranyl) propanoic acid, was synthesized from trans-4-hydroxy-L-proline.

The crystal and molecular structure of 3-[(5S)-5-carboxy-2-oxotetrahydrofur-5-yl]-(2S)-alanine (lycoperdic acid)

The crystal and molecular structure of 3-[(5<i>S</i>)-5-carboxy-2-oxotetrahydrofur-5-yl]-(2<i>S</i>)-alanine (lycoperdic acid)

Enzymatic formation of homocitric acid, an intermediate in lysine biosynthesis

Negishi cross-coupling of the silyl-protected 3-bromoenol of 1,2-cyclopentanedione with primary and secondary alkylzinc reagents using Pd-catalysts affords 3-alkyl substituted 1,2-cyclopentanediones in good yield. The method was applied to obtain 3-methylalkoxycarbonyl- and 3(2-Boc-aminoethyl)-alkoxycarbonyl-1,2-cyclopentanediones—homocitric and lycoperdic acid precursors. Homocitric and lycoperdic acids were synthesized using asymmetric oxidation with the Ti(OiPr)4/tartaric ester/tBuOOH complex in two steps from the obtained precursors.