14002-99-4Relevant academic research and scientific papers
Synthesis of coumarins by Pt-catalyzed hydroarylation of propiolic acids with phenols
Oyamada, Juzo,Kitamura, Tsugio
, p. 6918 - 6925 (2007/10/03)
Synthesis of coumarins from phenols and propiolic acids was examined by using a Pt catalyst such as PtCl2/AgOTf, K2PtCl4/AgOTf, and K2PtCl4/AgOAc. Propiolic acid reacted even with less reactive phenols in trifluoroacetic acid to give coumarins and dihydrocoumarins. In the case of substituted propiolic acids, phenylpropiolic acid and 2-octynoic acid, the reactions proceeded selectively to afford coumarins in good to high yields.
The effect of phenyl substituents on the release rates of esterase-sensitive coumarin-based prodrugs
Liao,Hendrata,Sung Yong Bae,Wang
, p. 1138 - 1147 (2007/10/03)
A coumarin-based prodrug system has been recently developed in our laboratory for the preparation of esterase-sensitive prodrugs of amines, peptides, and peptidomimetics. The drug release rates from this prodrug system were found to be dependent on the structural features of the drug moiety. In certain cases, the release can be undesirably slow for drugs that are secondary amines with relatively high pK(a)'s. Aimed at finding ways to manipulate the release rates to suit the need of different drugs, we have examined the effect of the phenyl ring substitutions on the release kinetics of such prodrugs and found that appropriately positioned alkyl substituents on the phenyl ring could help to facilitate the release by as much as 16-fold. Therefore, introduction of alkyl substituents on the phenyl ring should allow us to manipulate the release rates and, therefore, time profiles for different drugs.
Substituted coumarins as esterase-sensitive prodrug moieties with improved release rates
Liao, Yuan,Wang, Binghe
, p. 1795 - 1800 (2007/10/03)
Our laboratory has recently reported a coumarin-based prodrug system for the preparation of esterase-sensitive prodrugs of amines, peptides, and peptidomimetics. However, the release from this prodrug system was undesirably slow for some drug moieties. In this report, we describe the synthesis and evaluation of several substituted coumarin-based prodrugs of model amines with significantly increased release rates.
Lithiation in Flavones, Chromones, Coumarins, and Benzofuran Derivatives
Costa, Ana M. B. S. R. C. S.,Dean, Francis M.,Jones, Michael A.,Varma, Rajender S.
, p. 799 - 808 (2007/10/02)
Flavones are lithiated at position 3 by lithium di-isopropylamide in tetrahydrofuran at -78 deg C and the products are stable at that temperature.Appropriate reagents replace the lithium by carboxy, ethoxycarbonyl, mercapto, methylthio, trimethylsilyl, hydroxy, and other groups, sometimes giving products not previously available.Benzofurans are preferentially lithiated at position 2 if this is free, and may not be attacked if it is blocked, but if there is an activating group (i.e., one able to co-ordinate with the lithium cation) at position 2, then lithiation occurs at position 3.In the benzofuran series ring-opening is easier and lithiation often leads directly to acetylenic phenols.Chromones can be lithiated at positions 2 and 3 depending upon the substitution pattern and whether the substituents are activating.Aurones are not easily deprotonated, and only the acetylenic phenol arising from ring opening was found in the one successful case.Coumarins tend to behave simply as esters and give amides with the lithiating reagent, but 4-methoxycoumarin is readily lithiated at position 3.It is suggested that 3-deprotonation in ethers occurs easily only when there is an ether link antiperiplanar to the proton removed, and that the lithiated species are really unstable intermediates in trans-eliminations leading to alkyne derivatives.
SYNTHESIS OF SUBSTITUTED 4-(METHOXYPHENYL)-3,4-DIHYDROCOUMARINS
Chenault, Jacques,Dupin, Jean-Francois E.
, p. 437 - 443 (2007/10/02)
In polyphosphoric acid (PPA), 2- and 4-methoxycinnamic acids react with various dimethylphenols to give 4-phenyl-3,4-dihydrocoumarins by direct cycloaddition, whereas 3-methoxycinnamic acid, in the same conditions, also gives a flavanone formed by Fries rearrangement from a hydroxychalcone.These results are discussed in terms of electronic effects due to the methoxy substituents on the cinnamic acid.
β-Deprotonation by Lithium Di-isopropylamide. Vinyl Carbanions from Oxygen Heterocycles in the Synthesis of Carboxylic Acids in the Benzofuran, Flavone, and Coumarin Series and in the Regiospecific Acylation of 2,6-Dimethylchromone
Costa, Ana M. B. S. R. C. S.,Dean, Francis M.,Jones, Michael A.,Smith, Dennis A.,Varma, Rajender S.
, p. 1224 - 1226 (2007/10/02)
Lithium di-isopropylamide at -70 deg C can remove the α-proton from benzofuran in the absence of activating groups and the β-proton if such groups are present; in flavone and 4-methoxycoumarin β-deprotonation occurs readily and the carbanions are easily carboxylated giving acids not previously accessible, while in 2,6-dimethylchromone β-deprotonation is kinetically favoured allowing 3-acylation to be achieved separately from the conventional acylation at the 2-methyl group.
