Acyclic Keto Research Articles

N-(1-Deoxy-α-d-tagatopyranos-1-yl)-N-methylaniline (“d-Tagatose-N-methylaniline”)

Tagatosamines form in thermally-processed dairy products and contribute to the foods’ organoleptic and nutritional value. d-Tagatose-N-methylaniline (N-(1-deoxy-d-tagatos-1-yl)-N-methylaniline, 1-deoxy-1-(N-methylphenylamino)-d-tagatose) was synthesized from d-galactose via the Amadori rearrangement. In aqueous solution, it established an anomeric equilibrium consisting of 62.8% α-pyranose, 21.3% β-pyranose, 1.5% α-furanose, 8.1% β-furanose, and 6.2% acyclic keto tautomer. The crystalline α-pyranose anomer of d-tagatose-N-methylaniline adopted the 5C2 chair conformation. All hydroxyl and ring oxygen atoms and the amino nitrogen are involved in an extensive H-bonding network dominated by infinite homodromic chains. The Hirshfeld surface analysis suggests a significant contribution of non-polar intermolecular contacts to the crystal structure.

1-Deoxy-1-(N-methyl-4-fluorophenylamino)-D-arabino-hexulose

The title compound, C13H18FNO5, consists of D-fructose with an aromatic amine. The carbohydrate chain is in the acyclic keto form and has the zigzag conformation, while the solid-state NMR data suggests a conformational dimorphism at the aromatic amine group. The carbohydrate portion is involved in extensive O—H...O hydrogen bonding, which forms a two-dimensional network parallel to (001) and organized into fused homodromic ring patterns. The Hirshfeld surface fingerprint plots reveal a major contribution of the non-polar H...H and C...H interactions to the crystal packing forces.

Molecular and crystal structure and the Hirshfeld surface analysis of 1-amino-1-deoxy-α-d-sorbopyranose and 1-amino-1-deoxy-α-d-psicopyranose (“d-sorbosamine” and “d-psicosamine”) derivatives

Sorbosamine and psicosamine are the last two 1-amino-1-deoxy-hexuloses for which no structural data were available. We report on a13C NMR and a single crystal X-ray diffraction study of 1-deoxy-1-(N-methylphenylamino)-d-sorbose (1) and 1-deoxy-1-(N-methylphenylamino)-d-psicose (2). In solutions, both aminosugars are conformationally unstable and establish equilibria, with 90.7% α-pyranose, 3.8% α-furanose, 1.0% β-pyranose, 0.5% β-furanose, and 4.0% acyclic keto form for 1 and 32.4% α-furanose, 27.2% α-pyranose, 21.0% β-pyranose, 9.1% β-furanose, and 11.0% acyclic keto form for 2. X-ray diffraction data provided detailed structural information on 1 and 2 in the α-pyranose form. Both molecules adopt the 5C2 ring conformations, the bond distances and valence angles compare well with respective pyranose structures. All hydroxyl groups in crystal structures of both 1 and 2 participate in two-dimensional hydrogen bonding networks, the H-bonding pattern in 1 is dominated by co-crystallized water molecules. The Hirshfeld surface analysis revealed a significant contribution of non- or weakly polar interactions to the packing forces for both molecules, with crystal structure of 2 featuring short H⋯H contacts. Other structural features found in 2 are a significant planarity of the tertiary amino group (the pyramid heights are 0.127 Å in 2 vs 0.231 Å in 1), a concomitant non-involvement of the amine nitrogen in heteroatom contacts, and a unique anti-periplanar conformation around the C1C2 bond.

Crystal structure of the acyclic form of 1-de-oxy-1-[(4-methoxyphenyl)(methyl)amino]-d-fructose.

The title compound, C14H21NO6, (I), crystallizes exclusively in the acyclic keto form. In solution of (I), the acyclic tautomer represents only 10% of the population in equilibrium, with the other 90% consisting of β-pyran-ose, β-furan-ose, α-pyran-ose, and α-furan-ose cyclic forms. The carbohydrate chain in (I) has a zigzag conformation and the aromatic amine group has a transitional sp2/sp3 geometry. Bond lengths and valence angles in the carbohydrate portion compare well with the average values for related acyclic polyol structures. All of the hydroxyl groups are involved in inter-molecular hydrogen bonding and form a two-dimensional network of infinite chains, which are inter-linked by intra-molecular hydrogen bonds and organized into R88(16) homodromic ring patterns. A comparative Hirshfeld surfaces analysis of (I) and four other 1-amino-1-de-oxy-d-fructose derivatives suggests the balance of hydro-philic/hydro-phobic inter-actions plays a role in the crystal packing, favoring the acyclic isomer.

ChemInform Abstract: Template Catalysis by Metal—Ligand Cooperation. C—C Bond Formation via Conjugate Addition of Non‐Activated Nitriles under Mild, Base‐Free Conditions Catalyzed by a Manganese Pincer Complex.

AbstractThe title transformation proves efficient for the Michael addition of non‐activated aliphatic nitriles onto α,β‐unsaturated carbonyl compounds, including ester and cyclic or acyclic keto derivatives.

Structure–reactivity relationship of Amadori rearrangement products compared to related ketoses

Structure-reactivity relationships of Amadori rearrangement products compared to their related ketoses were derived from multiple NMR spectroscopic techniques. Besides structure elucidation of six Amadori rearrangement products derived from d-glucose and d-galactose with l-alanine, l-phenylalanine and l-proline, especially quantitative 13C selective saturation transfer NMR spectroscopy was applied to deduce information on isomeric systems. It could be shown exemplarily that the Amadori compound N-(1-deoxy-d-fructos-1-yl)-l-proline exhibits much higher isomerisation rates than d-fructose, which can be explained by C-1 substituent mediated intramolecular catalysis. In combination with a reduced carbonyl activity of Amadori compounds compared to their related ketoses which results in an increased acyclic keto isomer concentration, the results on isomerisation dynamics lead to a highly significant increased reactivity of Amadori compounds. This can be clearly seen, comparing approximated carbohydrate milieu stability time constants (ACuSTiC) which is 1 s for N-(1-deoxy-d-fructos-1-yl)-l-proline and 10 s for d-fructose at pD 4.20 ± 0.05 at 350 K. In addition, first NMR spectroscopic data are provided, which prove that α-pyranose of (amino acid substituted) d-fructose adopts both, 2C5 and 5C2 conformation.

ChemInform Abstract: Rhodium‐Catalyzed Oxidative Perfluoroalkenylation by Carbonyl Group Directed C—H Bond Activation.

AbstractA broad spectrum of substrates bearing a cyclic or acyclic keto function can be used in the title reaction with esters (II), (VII), and (XVIII).

Phytotoxins produced by the oak pathogen Discula quercina

SummaryTwo phytotoxic metabolites, p‐hydroxybenzaldehyde and indol‐3‐aldehyde, were isolated and identified by spectroscopic methods from solid cultures of Discula quercina, an endophytic fungal pathogen frequently associated with oak decline in Italy. In addition, the fungus produced an unusual acyclic keto acid as a major metabolite, which was identified by spectroscopic and chemical methods as 5‐oxo‐6E,8E‐octadecadienoic acid. In leaf puncture assays on Quercus suber and Q. ilex leaves, indol‐3‐aldehyde proved to be more toxic than p‐hydroxybenzaldehyde, while 5‐oxo‐6E,8E‐octadecadienoic acid was inactive even at the highest concentration used (1 mg ml−1). Although indol‐3‐aldehyde is a known microbial metabolite, its phytotoxic activity has hitherto not been reported. This report is the first to describe the production of phytotoxic compounds by D. quercina.

ChemInform Abstract: Ethynyl‐1,2‐benziodoxol‐3(1H)‐one (EBX): An Exceptional Reagent for the Ethynylation of Keto, Cyano, and Nitro Esters.

AbstractIn situ desilylation of reagent (II) generates a highly reactive ethynylation species which is successfully applied in the acetylene transfer towards various cyclic and acyclic keto, cyano and nitro esters.

Disordered hydrogen bonding in N-(1-deoxy-β- d-fructopyranos-1-yl)- N-allylaniline

We report on a 13C NMR and a single-crystal X-ray diffraction study of N-(1-deoxy-β- d-fructopyranos-1-yl)- N-allylaniline ( d-fructose- N-allylaniline). In solution, an equilibrium of α-pyranose, β-pyranose, α-furanose, β-furanose, and acyclic keto tautomers of the carbohydrate was detected in the following respective proportions: 2.2%, 47.4%, 4.5%, 33.6%, and 12.3%. In the crystalline state, the compound exists exclusively as the β-pyranose form, in the normal 2 C 5 chair conformation. Bond lengths and valence angles compare well with the average values from a number of β-fructopyranose derivatives. The structure displays two unusual features for this class of compounds. First, the molecule assumes an eclipsed conformation around the C1–C2 bond, apparently stabilized by an intramolecular O2–H···N hydrogen bond. Second, the O3, O4, and O5 hydroxyl groups are involved in an intermolecular hydrogen bonding, which forms 12-membered homodromic cycles. In the cycles, each determined hydrogen atom site is half occupied, possibly due to the ···H–O···H–O··· ⇌ ···O–H···O–H··· flip-flop type disorder.

Samarium(II) iodide-induced cascade reaction for tricyclic γ-lactone synthesis from acyclic keto diesters

Cascade reaction involving reductive cyclization, Dieckmann condensation, and lactonization of E- and Z-dimethyl 2-methyl-8-oxoundec-2-enedioates and Z-dimethyl 2-methyl-7-oxodec-2-enedioate with samarium(II) iodide was found to stereospecifically produce cis and trans bicyclo[4.4.0]decane (decalin) ring systems and trans bicyclo[4.3.0]nonan (perhydroindane) ring system each consisting of γ-lactone, respectively.

13C-Labeled N-Acetyl-neuraminic Acid in Aqueous Solution: Detection and Quantification of Acyclic Keto, Keto Hydrate, and Enol Forms by 13C NMR Spectroscopy

Aqueous solutions of N-acetyl-neuraminic acid (Neu5Ac, 1) labeled with (13)C at C1, C2, and/or C3 were analyzed by (13)C NMR spectroscopy to detect and quantify the acyclic forms (keto, keto hydrate, enol) present at varying pHs. In addition to pyranoses, solutions contained the keto form, based on the detection of C2 signals at approximately 198 ppm (approximately 0.7% at pH 2). Spectra of [2-(13)C] and [3-(13)C] isotopomers contained signals arising from labeled carbons at approximately 143 and approximately 120 ppm, respectively, which were attributed to enol forms. Solution studies of [1,2,3-(13)C3] 1 substantiated the presence of enol (approximately 0.5% at pH 2). Enol was not detected at pH > 6.0. A C2 signal observed at approximately 94 ppm was identified as C2 of the keto hydrate (approximately 1.9% at pH 2), based partly on its abundance as a function of solution pH. Density functional theory (DFT) calculations were used to study the effect of enol and hydrate structure on J(CH) and J(CC) values involving C2 and C3 of these forms. Solvated DFT calculations showed that (2)J(C2,H3) in cis and trans enols have similar magnitudes but opposite signs, making this J-coupling potentially useful to distinguish enol configurations. Solvent deuterium exchange studies of 1 showed rapid incorporation of (2)H from (2)H2O at H3 axial in the pyranoses at p(2)H 8.0, followed by slower exchange at H3 equatorial. The acyclic keto form, which presumably participates in this reaction, must assume a pseudo-cyclic conformation in solution in order to account for the exchange selectivity. Weak (13)C signals arising from labeled species were also observed consistently and reproducibly in aqueous solutions of (13)C-labeled 1, possibly arising from products of lactonization or intermolecular esterification.

Toward the total synthesis of ritterazine N

AbstractZr-mediated equilibrating cyclocarbonylation of a designed triene led with high diastereocontrol to the ABC 6-6-5 tricyclic core of ritterazine N. The 5-5 EF spiroketal side chain of ritterazine N was prepared by equilibrating cyclization of an acyclic keto diol. The two components were coupled, and the D ring was assembled by intramolecular aldol condensation.

The photoreactivity of the caged precursors of oligonucleotides containing C4'-oxidized abasic site and reaction of the generated lesion

The C4'-oxidized abasic site (1) is one of the oxidatively damaged DNA lesions by antitumor bleomycins (BLMs) and the acyclic keto aldehyde incorporated in DNA might react with DNA interacting biomolecules. We synthesized oligodeoxynuceotides 3-caged-1 and 3-caged-2 as caged precursors of 3, an ODN containing 1, to study the reactivities of 3 with amine. Irradiation of double stranded 3-caged-1 led to efficient formation of 3 compared to its single stranded form. Similarly, 3-caged-2 and its duplex afforded 3. With 3-caged-2, yields of 3 were lower compared to 3-caged-1. Formation of the duplex slowed decaging rate down but the yield of 3 was higher than that of single stranded 3-cage-2. Reaction of the obtained 3 with amine resulted in the formation of lactam 2b in good yield.

Induced Fit Movements and Metal Cofactor Selectivity of Class II Aldolases: STRUCTURE OF THERMUS AQUATICUS FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE

Fructose-1,6-bisphosphate (FBP) aldolase is an essential glycolytic enzyme that reversibly cleaves its ketohexose substrate into triose phosphates. Here we report the crystal structure of a metallo-dependent or class II FBP aldolase from an extreme thermophile, Thermus aquaticus (Taq). The quaternary structure reveals a tetramer composed of two dimers related by a 2-fold axis. Taq FBP aldolase subunits exhibit two distinct conformational states corresponding to loop regions that are in either open or closed position with respect to the active site. Loop closure remodels the disposition of chelating active site histidine residues. In subunits corresponding to the open conformation, the metal cofactor, Co(2+), is sequestered in the active site, whereas for subunits in the closed conformation, the metal cation exchanges between two mutually exclusive binding loci, corresponding to a site at the active site surface and an interior site vicinal to the metal-binding site in the open conformation. Cofactor site exchange is mediated by rotations of the chelating histidine side chains that are coupled to the prior conformational change of loop closure. Sulfate anions are consistent with the location of the phosphate-binding sites of the FBP substrate and determine not only the previously unknown second phosphate-binding site but also provide a mechanism that regulates loop closure during catalysis. Modeling of FBP substrate into the active site is consistent with binding by the acyclic keto form, a minor solution species, and with the metal cofactor mediating keto bond polarization. The Taq FBP aldolase structure suggests a structural basis for different metal cofactor specificity than in Escherichia coli FBP aldolase structures, and we discuss its potential role during catalysis. Comparison with the E. coli structure also indicates a structural basis for thermostability by Taq FBP aldolase.

Acyclic tautomers in crystalline carbohydrates: the keto forms of 1-deoxy-1-carboxymethylamino-D-2-pentuloses (pentulose-glycines).

NMR and X-ray diffraction studies on acyclic carbohydrate keto tautomers of N-(1-deoxy-d-erythro-2-pentulos-1-yl)- and N-(1-deoxy-d-threo-2-pentulos-1-yl)glycines (ribulose-glycine, 1 and xylulose-glycine, 2), are reported. In aqueous solutions, both 1 and 2 exist as a tautomeric mixture, with the beta-furanose as a major form, followed by the alpha-furanose and the acyclic keto tautomer. Both 1 and 2 crystallize as zwitterions in the acyclic keto form. Solid-state 13C NMR spectra reveal the existence of two crystallographically independent molecules in 2 but only one in crystalline 1. The structure of 2 was solved by X-ray diffraction; in the crystal, two conformational isomers, 2a and 2b in a 1:1 ratio, were identified. The conformers are packed in stacks of similar molecules, with a system of intermolecular hydrogen bonds involving all hydroxyl, ammonium, and carboxyl groups. The structural data indicate that the sugar portion of acyclic 2 adopts conformations similar to those proposed for the parent d-xylulose.

Synthesis of Some 3-Furylamine Derivatives

A general and efficient method for the synthesis of 3-furylamines via Michael addition of amines to acyclic keto alkynol precursors has been achieved. The preparation of various 3-furylamines has been carried out using a flexible methodology which also allows modification of the substituent at the 5-position.

Constituents of Lepidium meyenii ‘maca’

The tubers of Lepidium meyenii contain the benzylated derivative of 1,2-dihydro- N-hydroxypyridine, named macaridine, together with the benzylated alkamides (macamides), N-benzyl-5-oxo-6 E,8 E-octadecadienamide and N-benzylhexadecanamide, as well as the acyclic keto acid, 5-oxo-6 E,8 E-octadecadienoic acid. The structure elucidation of the isolated compounds was based primarily on 1D and 2D NMR spectroscopic analyses, including 1H– 1H COSY, 1H– 13C HMQC, 1H– 13C HMBC and 1H– 1H NOESY experiments, as well as from 1H– 15N NMR HMBC correlations for macaridine and N-benzylhexadecanamide.

A synthesis of the ring system of terpestacin

The ring system of the sesterterpene terpestacin has been obtained from a cyclopentanic precursor prepared from endo-3-bromocamphor and from an acyclic keto phosphonate prepared from 6-methylhept-5-en-2-one. The connection of both compounds has been achieved by a Horner-Wadsworth-Emmons reaction on the one hand and by a McMurry reaction on the other.

Highly stereoselective syntheses of spiroacetal enol ethers, ( E)- and ( Z)-methoxycarbonylmethylene-1, 6-dioxaspiro[4.5]decanes

( E)- and ( Z)-2-methoxycarbonylmethylene-1,6-dioxaspiro[4.5]decanes have been synthesized from an acyclic keto alcohol possessing an alkynoate part via intramolecular conjugate addition. Under thermodynamically controlled conditions using t-BuOK in THF, the ( E)-isomer could be obtained in 52:1 ratio. When a catalytic amount of Pd(OAc) 2 was used in benzene, the ( Z)-isomer could be obtained in 95:1 ratio.