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At least 1,153 records · Page 64Linked to original sources
PubMed2006

Biocatalytic synthesis of butein and sulfuretin by Aspergillus alliaceus.

Aspergillus alliaceus UI315 was examined for its potential to catalyze biotransformation reactions of chalcones that mimic plant biosynthetic processes. 3-(4' '-Hydroxyphenyl)-1-(2',4'-dihydroxyphenyl)propenone (4,2',4'-trihydroxychalcone, isoliquiritigein) (1) was efficiently transformed to two major metabolites that were isolated chromatographically and identified by spectroscopic methods as 3-(3' ',4' '-dihydroxyphenyl)-1-(2',4'-dihydroxyphenyl)propenone (butein) (7) and 2-[(3,4-dihydroxyphenyl)methylene]-6-hydroxy-3(2H)benzofuranone (7,3',4'-trihydroxyaurone, sulfuretin) (10). Inhibition experiments suggested that initial C-3 hydroxylation of 1 to 7 was catalyzed by a cytochrome P450 enzyme system. A second A. alliaceus enzyme, partially purified and identified as a catechol oxidase, catalyzed the oxidation of the catechol butein (7) likely through an ortho-quinone (8) that cyclized to the aurone product 10. This work showed that A. alliaceus UI315 contains oxidative enzyme systems capable of converting phenolic chalcones such as 1 into aurones such as 10 in a process that mimics plant biosynthetic pathways.

Aspergillus↗
PubMed1988

Facile N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the flavin-containing monooxygenase. A convenient synthesis of tritiated [methyl-3H]-4-phenyl-2,3-dihydropyridinium species.

A rapid, efficient procedure useful for the radiosynthesis of [Me-3H]-MPDP+ ([methyl-3H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me-3H]-MPTP to its corresponding radiolabeled N-oxide. For the small-scale synthesis required for radiolabeling procedures, this enzymatic process is superior to H2O2-mediated N-oxygenation of MPTP. In the presence of 0.5 mM NADPH, 4.5 mM n-octylamine, and 2 microCi [Me-3H]-MPTP, the only product detected in extracts from incubations performed with hog liver microsomes or purified hog liver flavin-containing monooxygenase is [Me-3H]-MPTP N-oxide. [Me-3H]-MPTP N-oxide is almost completely converted to [Me-3H]-MPDP+ by the action of trifluoroacetic anhydride. This procedure has the advantage of using a commercially available tritiated starting material, efficient transformations, and easily accomplished purification to afford a rapid synthesis of [Me-3H]-MPDP+.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Total synthesis of (-)-mniopetal E, a novel biologically intriguing drimane sesquiterpenoid.

We have achieved the total synthesis of (-)-mniopetal E, a drimane sesquiterpenoid which inhibits the reverse transcriptase of human immunodeficiency virus (HIV)-1. Our enantiospecific total synthesis of this target molecule in naturally occurring form commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy. The key steps of our total synthesis were as follows: (1) a combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations for construction of a butenolide tethering a 1,2,4, 9-functionalized nona-5,7-diene moiety at the beta-carbon, (2) stereoselective thermal intramolecular Diels-Alder reaction of the thus-formed trienic compound, providing preferentially an endo-cycloadduct with the desired pi-facial selection, and (3) efficient transformation of the gamma-lactone moiety in the major cycloadduct to the gamma-hydroxy-gamma-lactone part in mniopetal E. Our total synthesis of (-)-mniopetal E established the unsettled absolute stereochemistry of the antibiotic.

Anti-HIV Agents↗
PubMed2001

Dynamic kinetic resolution of beta-azido alcohols. An efficient route to chiral aziridines and beta-amino alcohols.

Enzymatic resolution of beta-azido alcohols in combination with ruthenium-catalyzed alcohol isomerization led to a successful dynamic kinetic resolution. A variety of racemic beta-azido alcohols were efficiently transformed to the corresponding enantiomerically pure acetates (ee up to 99% and conversion up to 98%). The synthetic utility of this procedure has been illustrated by the practical synthesis of (S)-propanolol I and (R)-beta-azido-alpha-(4-methoxyphenyl)ethanol ((R)-1c), a direct precursor of denopamine II.

Journal Article↗
PubMed2002

Diastereo- and enantioselective direct catalytic aldol reaction of 2-hydroxyacetophenones with aldehydes promoted by a heteropolymetallic complex: catalytic asymmetric synthesis of anti-1,2-diols.

An anti-selective direct catalytic asymmetric aldol reaction of 2-hydroxyacetophenones with aldehydes is described. The reaction is catalyzed by a heteropolymetallic complex to afford anti-alpha,beta-dihydroxy ketones as the major diastereomer with excellent enantioselectivity. The use of 2-hydroxyacetophenones bearing electron-donating groups at the phenyl moiety enabled efficient transformation of the aldol products (alpha,beta-dihydroxy ketones) into the corresponding alpha,beta-dihydroxy ester derivatives via Baeyer-Villiger oxidation. A plausible reaction mechanism is also discussed based on the stereochemistry of the products.

Journal Article↗
PubMed2002

Cyclic alkenenitriles: chemoselective oxonitrile cyclizations.

Potassium tert-butoxide triggers the chemoselective cyclization between nitrile anions and remote, enolizable carbonyl groups, despite the acidity difference favoring enolate formation and addition to the nitrile group. Domino deprotonation, cyclization, and dehydration efficiently transform a diverse array of omega-oxonitriles into carbocyclic and heterocyclic five- and six-membered alkenenitriles in a single synthetic operation.

Journal Article↗
PubMed2003

An efficient route to chiral alpha- and beta-hydroxyalkanephosphonates.

Enzymatic kinetic resolution of alpha- and beta-hydroxyphosphonates in combination with ruthenium-catalyzed alcohol isomerization led to a successful dynamic kinetic resolution. A variety of racemic hydroxyphosphonates were efficiently transformed to the corresponding enantiomerically pure acetates (ee up to 99% and yield up to 87%).

Journal Article↗
PubMed2005

Selective partial reduction of various heteroaromatic compounds with bridgehead nitrogen via Birch reduction protocol.

[reaction: see text] For the first time various heteroaromatic compounds with bridgehead nitrogen, including indolizines, bispyrrolopyrimidines, pyrroloquinolines, pyrroloisoquinolines, and bispyrrolopyrazines, were selectively partially reduced under Birch reduction conditions. It was found that the double bond in the fused heterocycles which possesses the highest LUMO density can be selectively reduced under these conditions. Indolizine 6, containing an ester group at C-6, was reductively alkylated to give dihydroindolizines 8 and 9 possessing a quaternary carbon center in good yield. It was found that ambident substrate 12, under Birch reduction conditions, underwent smooth partial reduction to give 4,5-dihydroquinoline 14 as a sole product with no evidence of reduction of the side chain olefin. It was also shown that electron-rich pyrroloisoquinoline 15, which cannot be reduced via catalytic hydrogenation conditions, was efficiently transformed into its dihydrocounterpart 16 by using the Birch reduction protocol. Finally, it was shown that various fused diazines were smoothly and stereoselectively reduced under Birch reduction conditions to give trans-4,5-disubstituted dihydropyrimidines 30 and 32 in virtually quantitative yields.

Heterocyclic Compounds, 3-Ring↗
PubMed2005

Novel approach to 5-substituted proline derivatives using a silver-catalyzed cyclization as the key step.

A novel synthetic approach to the synthesis of enantiomerically pure 2,5-disubstituted pyrrolines is described. The methodology involves a Ag-catalyzed 5-endo-dig cyclization of enantiopure aryl-substituted acetylene-containing amino acids. It has also been shown that the obtained pyrrolines can be efficiently transformed into the corresponding saturated 5-aryl-substituted proline derivatives.

Catalysis↗
PubMed2005

Reductive cleavage of tetrahydrofuryl sulfur-substituted oxiranes: application to the formal synthesis of Kumausyne and Kumausallene.

[reactions: see text] Readily available sulfinyl and sulfonyl tetrahydrofuran methanol derivatives have been transformed efficiently into a variety of substituted tetrahydrofuryl alcohols by treatment with (PhSe)2 in the presence of an excess of NaBH4. Alternatively, oxirane cleavage with MgI2 produces the related ketones, amenable to stereocontrolled reduction. This reductive cleavage methodology has been applied to short formal syntheses of trans-Kumausyne and Kumausallene.

Journal Article↗
PubMed2006

Proline-catalyzed, asymmetric mannich reactions in the synthesis of a DPP-IV inhibitor.

[reaction: see text] A highly stereoselective L-proline-catalyzed, asymmetric direct Mannich reaction between a glyoxalate-derived imine and phenyl acetaldehyde was employed for the formation of a syn substituted beta-phenyl homoserine. This Mannich adduct was then readily elaborated to a functionalized beta-phenyl aspartic acid derivative through a series of mild and efficient transformations.

Aldehydes↗
PubMed2006

Divergent asymmetric synthesis of 3,5-disubstituted piperidines.

A divergent synthesis of various 3,5-dioxygenated piperidines with interesting pharmacological properties is described. A mixture of the achiral cis- and racemic trans-3,5-piperidine diol could be efficiently obtained from N-benzylglycinate in five steps by the use of chemoenzymatic methods. In the subsequent enzyme- and Ru-catalyzed reaction, the rac/meso diol mixture was efficiently transformed to the cis-(3R,5S)-diacetate with excellent diastereoselectivity and in high yield. Further transformations of the cis-diacetate selectively delivered the cis-piperidine diol and the cis-(3R,5S)-hydroxy acetate. Alternatively, the DYKAT could be stopped at the monoacetate stage to give the trans-(3R,5R)-hydroxy acetate.

Acetates↗
PubMed1996

Novel Dendritic alpha-Sialosides: Synthesis of Glycodendrimers Based on a 3,3'-Iminobis(propylamine) Core.

The cluster or multivalent effect has been recognized as an effective means by which to increase binding interactions between carbohydrates and proteins. In fact, it has been demonstrated that sialylated multibranched L-lysine dendrimers were potent inhibitors of hemagglutination of human erythrocytes by Influenza viruses. In a continuation of these studies, the synthesis of novel glycodendrimers with even valencies from 2 to 16 and ending with equidistant thiosialoside residues is described. These symmetrical dendrimers were more readily characterized by standard NMR spectral techniques than previously reported nonsymmetrical dendrimers of this general type. The synthesis of the dendritic core was based on the regioselective protection of the primary amines of 3,3'-iminobis(propylamine) (4) using benzyl cyanoformate. The resulting secondary amine 5 was alkylated with tert-butyl bromoacetate to provide divalent core structure 6 with Cbz protected amines and acid protected tert-butyl ester. Sequential deprotection by trifluoroacetolysis or hydrogenation afforded acid 7 or diamine 8 as key precursors, respectively. The two fragments were coupled using HOBt/DIC strategy to provide Cbz-protected dendrimers with valencies of 2, 4, 8, and 16 in the first, second, third, and fourth generations, respectively, in reasonable to good yields (42-82%). Cbz-protected precursors were efficiently transformed into N-chloroacetylated dendrimers by hydrogenolysis and treatment of the resulting amines with chloroacetic anhydride (82-91%). N-Chloroacetylated dendrimers were then treated with an excess of 2-thiosialic acid derivative 3 to give fully protected sialodendrimers in 76-96% yields. Deprotection of sialodendrimers under Zemplén conditions followed by methyl ester saponification and purification by gel permeation chromatography afforded symmetrical dendritic alpha-thiosialosides 21, 23, 25, and 27 in fair yields (47-58%). These novel sialodendrimers, in keeping with their design, are currently being evaluated as inhibitors of human erythrocyte hemagglutination by Influenza viruses.

Journal Article↗
PubMed1997

Highly Stereoselective Synthesis of Trifluoromethylated Compounds via Ester-Enolate [2,3]-Wittig and [3,3]-Ireland-Claisen Rearrangements.

gamma-Trifluoromethylated propargylic alcohols have been obtained in optically pure forms via effective enzymatic kinetic resolution and then converted into (E)- or (Z)-allylic alcohols. [2,3]-Wittig rearrangement of the corresponding [[gamma-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded alpha-hydroxy-beta-(trifluoromethyl)-gamma,delta-unsaturated carboxylic acid methyl esters in good yields. The rearrangement of (Z)-substrates proceeded in a highly stereoselective manner to give anti-isomers with E configuration at a newly created olefinic bond via complete chirality transfer. (E)-Substrates, however, showed relatively low stereoselectivities resulting in mixtures of syn- and anti-products. The trifluoromethylated allylic alcohols were also converted into the corresponding alpha-methoxyacetic acid gamma-(trifluoromethyl)allyl esters and evaluated as substrates for [3,3]-Ireland-Claisen rearrangement. (E)-Substrates were efficiently transformed into syn-products while (Z)-substrates exhibited relatively low stereoselectivities. The two complementary methods provide facile routes to highly functionalized trifluoromethyl-containing molecules with a high degree of stereocontrol.

Journal Article↗
PubMed1998

Formal Total Synthesis of Hemibrevetoxin B by an Oxiranyl Anion Strategy.

The synthesis of the tetracyclic structure of hemibrevetoxin B (1) was achieved through a linear approach involving sequential coupling of three kinds of sulfonyl-stabilized oxiranyl anions, 5b, 6b, and 7b, to the monocyclic tetrahydropyran 4 containing the requisite substituents. Two iterations of alkylation of an oxiranyl anion and 6-endo cyclization provided the 6,6,6-tricyclic ring system 34, which was efficiently transformed into the 6,6,7-ring system 35 by ring expansion using trimethylsilyldiazomethane. Installation of the final oxepane ring into 38 was carried out using a combination of the oxiranyl anion methodology and ring enlargement just described. Stereoselective introduction of a tertiary methyl group into 41 provided the tetracyclic compound 42a, which contains all the asymmetric centers of 1. Elaboration of 42a to the known compound 2, which was already transformed into hemibrevetoxin B, completed the formal total synthesis of the natural product.

Journal Article↗
PubMed2000

Sharpless asymmetric dihydroxylation of 5-aryl-2-vinylfurans: application to the synthesis of the spiroketal moiety of papulacandin D.

[formula: see text] Using the Sharpless catalytic asymmetric dihydroxylation reaction on 5-aryl-2-vinylfurans, diols are produced in high enantioexcess. The resulting diols can be efficiently transformed into the spiroketal ring precursor of the antifungal compound papulacandin D. Stereoselective reduction of this precursor followed by a diastereoselective dihydroxylation completes the synthesis of a mannopyranoside isomer of a papulacandin derivative.

Aminoglycosides↗
PubMed2001

Direct catalytic enantio- and diastereoselective aldol reaction using a Zn-Zn-linked-BINOL complex: a practical synthesis of syn-1,2-diols.

[reaction: see text] The direct catalytic enantio- and diastereoselective aldol reaction with 2-hydroxy-2'-methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked-BINOL complex 2, to afford alpha,beta-dihydroxy ketones in a highly syn-selective manner (up to syn/anti 97/3) and in excellent yields (up to 95%) and ees (up to 99%). Efficient transformations of the alpha,beta-dihydroxy ketone into an alpha,beta-dihydroxy ester and an alpha,beta-dihydroxy amide via regioselective rearrangements are also described.

Journal Article↗