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To gain comprehensive insight into the interactions of key coffee odorants, like the Strecker aldehydes, acetaldehyde, propanal, methylpropanal, 2- and 3-methylbutanal, and methional, and the nonvolatile fraction of coffee, an untargeted metabolomics approach was applied. Ultra performance liquid chromatography (UPLC)-time of flight (TOF)-mass spectrometry (ESI-) profiling followed by statistical data analysis revealed a marker substance for a coffee beverage spiked with acetaldehyde with an accurate mass of 217.0703 [M - H]-. This compound could be identified as a reaction product of quinic acid (QA) and acetaldehyde linked by acetalization at the cis-diol function of QA. Consequently, the acetalization of aldehydes, QA, 5-O-caffeoyl quinic acid (CQA), and quinic acid γ-lactone (QAL) was investigated by means of model reactions, followed by synthesis, isolation, and structure elucidation via UPLC-TOF-MS and 1D and 2D NMR techniques. UHPLC-MS/MSMRM screening and the quantification of aldehyde adducts in coffee beverages revealed the presence of QA/acetaldehyde, -/propanal, -/methylpropanal, and -/methional reaction products and CQA/acetaldehyde, -/propanal, -/methylpropanal, -/2- and 3-methylbutanal, and -/methional and QAL/acetaldehyde adducts for the first time, in concentrations of 12-270 μg/L for QA/aldehydes, 5-225 μg/L for CQA/aldehydes, and 62-173 μg/L for QAL/acetaldehyde. The sensory characterization of the identified compounds showed bitter taste recognition thresholds of 48-297 μmol/L for CQA adducts and 658 μmol/L for QAL/acetaldehyde, while the QA adducts showed no bitter taste (2000 μmol/L).

There is disclosed an oral pharmaceutical formulation of bitter compounds that are agonists of TAS2R receptors for the treatment of pulmonary hypertension (PAH). More specifically, there is disclosed a PAH oral formulation comprising a bitter agent selected from the group consisting of 3-caffeoylquinic-1,5-lactone (3-CQL), chlorogenic acid (CGA), denatonium benzoate (DB), denatonium chloride (DC), denatonium saccharide (DS), denatonium acetate (DA), and combinations thereof and a PDE-5 inhibitor.

There is disclosed an oral pharmaceutical formulation of bitter compounds that are agonists of taste receptor type 2 (TAS2R) receptors for the function of appetite suppression for the treatment of obesity. More specifically, the present disclosure provide

The synthesis of four isomers of p-coumaroylquinic acids was performed by esterification of p-acetylcoumaroylchloride with a suitably protected (?)-quinic acid. All isomers have been characterized by means of NMR spectroscopy and circular dichroism. Acyl migration was observed in the synthesis of 3-O-p-coumaroylquinic acid and 4-O-p-coumaroylquinic acid. Calculations on the most stable conformations of all isomers have also been performed to explain the acyl migration observed during the synthesis procedure.

A biomass-based route to the preparation of hydroquinone starting from the renewable starting material quinic acid is described. Amberlyst-15 in the dry form promoted the one-step formation of hydroquinone from quinic acid in toluene without any oxidants or metal catalysts in 72 % yield. Several acidic polymer-based resins and organic acids as promoters as well as a variety of reaction conditions were screened including temperature, concentration and low- and high-boiling-point solvents. A 1:4 (w/w) ratio of quinic acid/Amberlyst-15 was determined to be optimal to promote hydroquinone formation with only traces of a dimeric side-product. A mechanism has been proposed based on the decarbonylation of protonated quino-1,5-lactone that is supported by experimental and computational calculation data.

The present invention relates to a quinic acid lactone derivative preparation method, which comprises: in an organic solvent, carrying out a reaction with a compound 1 to obtain a compound 2. According to the method of the present invention, the solubility of the reactant in the solvent is increased so as to substantially improve the yield of the product and provide convenience and economy. The structures of the compounds 1 and 2 are defined in the specification.

Tri-3,4-dimethoxycinnamoyl-1,5-γ-quinide was synthesized and fully characterized by a direct synthesis from quinic acid and a large excess of 3,4-dimethoxycinnamoyl chloride. Mono-and di-3,4-dimethoxycinnamoyl-1,5-γ- quinides were also obtained from the direct coupling of 1,5-γ-quinide and 3,4-dimethoxycinnamoyl chloride in different molar ratios. Moreover, a hypothetical mechanism of the direct lactonization is proposed. Mono-, di-, and tri-3,4-dimethoxycinnamoyl-1,5-γ-quinides have been synthesized from 1,5-γ-quinide and 3,4-dimethoxycinnamoyl chloride in different molar ratios. The only triester quinide was also easily obtained by a direct synthesis from D-(-)-quinic acid in the presence of an excess of the acyl chloride. Copyright

The efficient synthesis of 3-, 4-, and 5-O-feruloylquinic acids starting from d-(-)-quinic acid is described. Esterification of suitably protected quinic acid derivatives with 3-(4-acetoxy-3-methoxyphenyl)-acryloyl chloride and subsequent hydrolysis of al

We report the first total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives, 3,5-O-diferuloylquinic acid and 3,5-(3,4-dimethoxycinnamyl)quinic acid, in a nine-step sequence. The key step involves Knoevenagel condensations between vanillin, 3,4-dimethoxybenzaldehyde or 4-hydroxy-3-methoxybenzaldehyde and the dimalonate ester of quinic acid.

This invention discloses 1-desoxy-2-methylene-19-nor-vitamin D analogs, and specifically (20S)-25-hydroxy-1-desoxy-2-methylene-19-nor-vitamin D3 and pharmaceutical uses therefor. This compound exhibits relatively high binding activity and prono

Disclosed are compounds comprising analogs of quinic acids or shikimic acids having anti-inflammatory properties. The compounds are suitable for oral administration, stable, and demonstrate significant efficacy in inhibiting NF-kB, inhibiting leukocyte ad

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we d

19-nor-vitamin D analogs having an additional heterocyclic ring connecting the 3β-oxygen and carbon-2 or the 1α-oxygen and carbon-2 of the A-ring of the analog, and pharmaceutical uses therefore, are described. These compounds exhibit significant activity

Selective mono-functionalization of 3-epi, 4-epi-, and 5-epi quinic and shikimic acid derivatives has been accomplished by enzymatic acylation with Candida antarctica lipase A (CAL-A). We propose that the selectivity of this lipase is related to both the

We have developed simple methods that provide a rapid entry into the synthesis of a series of quinate and shikimate analogues, including (-)-methyl 4-epi-shikimate and the 4,5-epoxy analogues of the parent acids. Epoxy derivatives of quinic and shikimic a

In a search for novel vitamin D compounds of potential therapeutic value, E- and Z-isomers of 1α,25-dihydroxy-2-(3′-hydroxypropylidene)-19- norvitamin D3, as well as a derivative of the former compound possessing a 3′-(methoxymethoxy)propyliden

This invention relates to the field of drug discovery. Specifically, it describes a method (“Inverted Drug Screening” or “IDS?”) of identifying therapeutics from ethnobotanical (EB) preparations by repeatedly fractionating and testing fractions from EB so

A search for noncarbohydrate sLex mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLex. The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

An enantiodivergent strategy for the total chemical synthesis of both (+)- and (-)-dragmacidin F beginning from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.

Methods for treating and preventing obesity, inhibiting adipocyte differentiation, inhibiting increased SCD-1 gene transcription, and/or reducing body fat in a subject include administering at least one analog of 1α,25-dihydroxyvitamin D3 or 1α

2-propylidene-19-nor-vitamin D compounds are disclosed as well as pharmaceutical uses for these compounds and methods of synthesizing these compounds. These compounds are characterized by high bone calcium mobilization activity and high intestinal calcium

The first total synthesis of (+)-dragmacidin F has been accomplished, establishing the absolute configuration of this biologically important, antiviral marine alkaloid. The convergent route described features a palladium-mediated oxidative pyrrole carbocy

Five gemini-type amphiphiles bearing cyclitol head groups, which have abundance of axial hydroxy groups, are newly synthesized. The syntheses are based on a common mixed anhydride method utilizing N,N′- [iminobis(trimethylene)]bisquinamide, prepared from

A series of indanotriazine C-ribosides were prepared as SAH mimics, and tested for their ability to inhibit erythromycin resistance methylases Erm AM and Erm C'. A carbocyclic analogue derived from quinic acid was also synthesized and tested. (C) 2000 Elsevier Science Ltd. All rights reserved.

A highly stereocontrolled synthesis of ring D/E precursor to reserpine has been developed starting from (-)-quinic acid as a chiral template. The total synthesis of (-)-reserpine is described through the cyclization of an immonium lactam intermediate.

(2R)-2-Bromodehydroquinic acid and (2R)-2-fluorodehydroquinic acid ? have each been synthesised in six steps from quinic acid via the common intermediate 6. The syntheses exploit the selective protection of the 4-hydroxy group of the quinic acid lactone 3 with tert-butyldimethylsilyl chloride. ? IUPAC names: (1S,2R,4S,5R)-2-bromo-1,4,5-trihydroxy-3-oxocyclohexanecarboxylic acid and (1S,2R,4S,5R)-2-fluoro-1,4,5-trihydroxy-3-oxocyclohexanecarboxylic acid, respectively.

D-(-)-Quinic acid (1) was converted to the fungal metabolites mycosporin I (2) and mycosporin-gly (13) via the iminophosphorane 64. The latter was prepared in 10 steps from 1 using oxidative bromination of quinide 33 to furnish 41. Reduction of the γ-lact

19-Nor-1α,25-dihydroxyvitamin D3 (2) was synthesized from A-ring precursor 5 and ketone 4.Two synthesis of 5 were studied; one starting from (-)-quinic acid as a template and one starting from cis-1,3,5-cyclohexanetriol via a chemoenzymatic approach.

Synthesis of 1-epi-dehydroquinate, 9, provided an authentic sample of this material and allowed its identification as a minor product in the noncatalyzed rearrangement of enolpyranose 4a to 3-dehydroquinate, 7 (3-DHQ) None of this isomer was detected in the product of the transformation of DAHp, 1 , to 3-DHQ catalyzed by dehydroquinate synthase. This result indicates that the enolpyranose 4a is not released from the enzyme active site prior to rearrangement to 3-DHQ, a possibility suggested previously (Bartlett, P.A.; Satake, K.J. Am. Chem. Soc. 1988, 110, 1628-1630). Enolpyranose 4a was generated in the presence of DHQ synthase; however, the formation of 9 was not diminished, indicating that spontaneous rearrangement is faster than uptake by the enzyme under these conditions. The question remains whether the enzyme takes an active role in catalyzing the rearrangement of 4a to 3-DHQ or simply provides a conformational template to prevent formation of the side product 9.

The racemate of 2,5-dihydro-3-hydroxymethyl-2,5-dimethoxy-2-methylfuran (11), prepared from the reaction of 3-hydroxymethyl-2-methylfuran (12b), with bromine in methanol, is converted into the racemate of 4-hydroxy-2-hydroxymethylcyclopent-2-en-1-one (9a) when heated in aqueous dioxan buffered at pH 6.3. Methyl quinate (17b), obtained by treating D-(-)-quinic acid (17a) with methanolic hydrogen chloride, reacts with ammonia in methanol to give quinamide (17c) which affords 1,1'-ON-isopropylidenequinamide (27a) in the presence of acetone containing hydrogen chloride.Benzoyl chloride in pyridine transforms compound (27a) into the 5-O-benzoate (27b) which undergoes selective hydrolysis in hot aqueous acetic acid to give 5-O-benzoyl-1,1'-ON-isopropylidenequinamide (26).Sequential treatment of compound (26) with sodium periodate in aqueous tetrahydrofuran (THF) and pyrrolidinium acetate in hot benzene affords (5R,8R)-8-benzoyloxy-2,2-dimethyl-4-oxo-3-azaspironon-6-ene-6-carbaldehyde (32).The aldehyde (32) is transformed into (5R,8R)-8-hydroxy-6-hydroxymethyl-2,2-dimethyl-1-oxa-3-azaspironon-6-en-4-one (34a) by reaction with sodium borohydride in THF followed by methanolic sodium methoxide.Hydrazinolysis of the oxazolidinone ring of the last-described compound is effected in boiling hydrazine hydrate to yield (1R,4R)-1,4-dihydroxy-2-hydroxymethylcyclopent-2-ene-1-carbohydrazide (35a).Treatment of the acid hydrazide (35a) with nitrous acid and thermolysis of the derived acid azide (35b) gives (4R)-4-hydroxy-2-hydroxymethylcyclopent-2-en-1-one (9a).