Ester 1b Research Articles

Synthesis of o-carborane-C-carboxylates of certain natural terpene alcohols, sterols, phenols, and camphar oxime

Previously unreported esters 1b–20b were synthesized from natural terpene alcohols, sterols, plant phenols, and camphar oxime (1a–20a) by reaction with o-carborane-C-carboxylic acid chloride.

Novel Water‐Soluble Poly(m‐benzamide)s: Precision Synthesis and Thermosensitivity in Aqueous Solution

AbstractSummary: Chain‐growth polycondensations of 3‐aminobenzoic acid methyl esters 1a and 1b, bearing a tri‐ or tetra(ethylene glycol) methyl ether unit on the amino group, respectively, were carried out with lithium hexamethyldisilazide (LiHMDS) as a base and phenyl 4‐methylbenzoate (2) as an initiator in THF at 0 °C. The poly(m‐benzamide)s obtained in the presence of N,N,N′,N′‐tetramethylethylenediamine (TMEDA) possessed narrow molecular weight distributions ($\overline M _{\rm w} /\overline M _{\rm n}$ < 1.2) with molecular weights that were determined by the feed ratios of [1]0/[2]0. Poly1a and poly1b were each soluble in water and exhibited a lower critical solution temperature (LCST) in water. Furthermore, the phase separation in water depended on the length of the oligo(ethylene glycol) side chain and on the molecular weight and molecular weight distribution of poly1.Thermally sensitive water‐soluble poly(m‐benzamide)s.magnified imageThermally sensitive water‐soluble poly(m‐benzamide)s.

Kaurene diterpenes from Laetia thamnia inhibit the growth of human cancer cells in vitro

Four ent-kaurene diterpenes were isolated from the leaves of Laetia thamnia L.: ent-kaur-16-en-19-oic acid ( 1a), ent−3β-hydroxykaur-16-ene ( 2), ent-kaur-16-en-3α,19-diol ( 3a), and ent-17-hydroxykaur-15-en-19-oic acid ( 4). The methyl ester ( 1b) of compound 1a and the acetate diester ( 3b) of compound 3a were prepared, and all compounds were evaluated for cytotoxicity against human prostate (22Rv1, LNCaP), colon (HT29, HCT116, SW480, SW620), and breast (MCF-7) tumor cells at concentrations ranging from 6 to 50 μg/mL. The kaurenes showed activity in all cell lines tested, with the prostate cells demonstrating the most sensitivity as follows: 22 Rv1 cells towards 1a (IC 50 5.03 μg/mL) and 1b (IC 50 6.81 μg/mL), and LNCaP towards 2 (IC 50 12.83 μg/mL) and 4 (IC 50 17.63 μg/mL).

“Living”/controlled polymerization of methyl acrylate mediated by dithiocarbamates under γ-ray irradiation

γ-Ray initiated reversible addition–fragmentation chain transfer (RAFT) polymerizations of methyl acrylate (MA) were investigated in bulk using five different dithiocarbamate structures, 2-phenyl-benzoimidazole-1-carbodithioic acid benzyl ester (1b), 2-methyl-benzoimidazole-1-carbodithioic acid benzyl ester (1c), 2-pheny-indole-1-cardithioic acid benzyl ester (1d), 2-(carbazole-9-carbothioylsulfanyl)-2-methyl-propionic acid ester (1e), and carbazole-9-carbodithioic acid naphthalene-1-ylmethyl ester (1f), as RAFT agents. The experiment results showed that MA polymerized in a controlled way under a low irradiation dose rate, i.e., first-order kinetic plots, the experimental molecular weights increased linearly with monomer conversions. The polydispersity indices of polymers generally remained at a relatively low value (lower than 1.4). The effect of irradiation dose on the polymerization results was investigated. The obtained polymers were characterized with 1H NMR and GPC. Chain-extension reaction was also successfully carried out using the obtained polymer as the macro-RAFT agent and styrene as the second monomer. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1769–1775, 2007

Application of the asymmetric hydrogenation of enamines to the preparation of a beta-amino acid pharmacophore

(3 R)-3-[ N-( tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 7a has been synthesized by an asymmetric hydrogenation of enamine ester 3 using chiral ferrocenyl ligands I and II in conjunction with [Rh(COD)Cl] 2. The direct reduction of 3 provides amino ester 1b in 93% ee, which was isolated as an ( S)-camphorsulfonic acid salt to upgrade the enantiomeric excess to >99%. A more concise approach was developed involving the in situ protection of 1b using di- tert-butyldicarbonate. This approach provided the desired N-Boc amino ester 7b directly from the hydrogenation with 97% ee, which was upgraded to >99% ee upon crystallization.

Highly Enantioselective Direct Reductive Coupling of Conjugated Alkynes and α-Ketoesters via Rhodium-Catalyzed Asymmetric Hydrogenation

Catalytic hydrogenation of 1,3-enynes 1a-7a in the presence of ethyl pyruvate and related activated ketones using chirally modified cationic rhodium catalysts results in reductive coupling to afford dienylated alpha-hydroxy esters 1b-7b and 3c-3f with exceptional levels of regio- and enantiocontrol. These studies represent the first highly enantioselective direct catalytic reductive couplings of alkynes to ketones. As illustrated by the conversion of 6b to 6c-6h, the diene containing the side chain of the coupling products is subject to diverse chemo- and regioselective manipulation. Reductive coupling of enyne 6a and ethyl pyruvate using elemental deuterium provides the monodeuterated product deuterio-6b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle, as corroborated by ESI-MS analysis.

Studies with Functionally Substituted Enamines: The Reactivity of Enaminals and Enamino Esters toward Naphthoquinone, Hydrazonoyl Halides, Aminoazoles and Hippuric Acid

Whereas enamines 1a,b react with naphthoquinone (2) to yield the naphthofuranals 5a,b, enamine ester 1c react with 2 to yield benzoindole derivatives 7. Enamine 1b reacts with hydrazonoyl halides 8 to yield 3,4-disubstituted pyrazoles 12. On the other hand, the enaminal 1a failed to react with 8, while enamine ester 1c afforded hydrazone 16 on treatment with 8. The enamino ester 1b afforded triethyl 1,3,5-benzenetricarboxylates on refluxing in acetic acid.

Sydnones as Masked Hydrazines for the Synthesis of 4‐Arylazo‐1,2‐dihydro‐pyrazol‐3‐one Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Conformational Studies on Hexa-O-alkyl p-Unsubstituted Calix[6]arenes

[structure: see text] In this article we describe the selective O-benzylation of para-unsubstituted calix[6]arene 1 in rings 1 and 4 (2a-c) and the subsequent alkylation of phenol groups with alpha-haloesters (methyl esters 3a, 3c, and 3e; tert-butyl esters 3b, 3d, and 3f) to determine the effect of these groups on their conformational behavior. 2D NMR studies at 188 K reveal that compounds 2a-c, 3b, 3d, and 3f are less flexible, showing a 1,2,3-alternate conformation. The same conformation has been observed in the solid state.

Hydrogen‐Mediated Reductive Coupling of Conjugated Alkynes with Ethyl (N‐Sulfinyl)iminoacetates: Synthesis of Unnatural α‐Amino Acids via Rhodium‐Catalyzed C—C Bond Forming Hydrogenation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Microwave‐Accelerated Esterification of α,β‐Unsaturated Acids with Alkyl or Aryl Carbonochloridate and Triethylamine in Acetonitrile as a Novel Esterifying Reagent Mixture.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sydnones as Masked Hydrazines for the Synthesis of 4‐Arylazo‐1,2‐dihydro‐pyrazol‐3‐one Derivatives

A simple and convenient one‐pot synthesis of 4‐(4‐chlorophenylazo)‐5‐methyl‐2‐aryl‐1,2‐dihydro‐pyrazol‐3‐ones (4a–j) has been carried out from 3‐arylsydnones (3a–j) by reaction with 2‐(4‐chlorophenyl)‐hydrazono‐3‐oxo‐butyric acid ethyl ester (2b). The 3‐arylsydnones are used as masked hydrazines in this reaction. Similarly, the 4‐arylazo‐2‐(7‐hydroxy‐4‐methyl‐2‐oxo‐2H‐chromen‐8‐ylmethyl)‐5‐methyl‐1,2‐dihydro‐pyrazol‐3‐ones (7a–j) were synthesized from 3‐[(7‐acetoxy‐4‐methyl‐8‐methylene)coumaryl]sydnone (5). All the newly synthesized compounds exhibited antimicrobial activity greater than the reference drugs used.

Highly Enantioselective Synthesis of (2S)-α-(Hydroxymethyl)-glutamic Acid by the Catalytic Michael Addition of 2-Naphthalen-1-yl-2-oxazoline-4-carboxylic Acid tert-Butyl Ester

[reaction: see text]. Highly enantioselective synthesis of a potent metabotropic receptor ligand, (2S)-alpha-(hydroxymethyl)-glutamic acid (2, HMG) was accomplished by the catalytic Michael addition of 2-naphthalen-1-yl-2-oxazoline-4-carboxylic acid tert-butyl ester (3b), using the phosphazene base, BEMP, in CH(2)Cl(2) at -60 degrees C in the presence of (S)-binaphthyl quaternary ammonium salt 4.

Antibacterial triterpenes from Syzygium guineense (Myrtaceae)

Antibacterial bioassay-guided fractionation of Syzygium guineense leaf extracts afforded 10 triterpenes, namely betulinic acid 1, oleanolic acid 2, a mixture of 2-hydroxyoleanolic acid 3a, 2-hydroxyursolic acid 3b, arjunolic acid 4a, asiatic acid 4b, a mixture of terminolic acid 5a, 6-hydroxyasiatic acid 5b, and a mixture of arjunolic acid 28-β-glucopyranosyl ester 6a and the asiatic acid 28-β-glucopyranosyl ester 6b. Isolated compounds were submitted to an antibacterial assay system against gram-positive and -negative bacteria and human pathogen bacteria. Compounds 4a and 4b showed the most significant antibacterial activity against Escherichia coli, Bacillus subtilis and Shigella sonnei. The fraction 5a– 5b was the least active, whereas compounds 1, 2 and the mixtures of 3a– 3b and 6a– 6b were inactive in the assays.

Synthesis and antitubercular activities of bis-glycosylated diamino alcohols

Conjugate addition of diamines to glycosyl olefinic esters 1a and 1b followed by reduction of resulting bis-glycosyl β-amino esters ( 2–7 and 14–19) with lithium aluminium hydride led to the respective glycosyl amino alcohols ( 8–13 and 20–25) in moderate to good yields. All the compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H 37Ra and H 37Rv. Few of the compounds exhibited antitubercular activity with MIC as low as 6.25–3.12 μg/mL in virulent and avirulent strains. Compound 13 was found to be active against MDR strain and showed mild protection in mice.

A Microwave‐Accelerated Esterification of α,β‐Unsaturated Acids with Alkyl or Aryl Carbonochloridate and Triethylamine in Acetonitrile as a Novel Esterifying Reagent Mixture

AbstractAn efficient synthesis of α,β‐unsaturated esters by treatment of the corresponding acids with alkyl or aryl carbonochloridate, triethylamine, and acetonitrile was accomplished for the first time under microwave irradiation for 10 min. The esters 1b–24b were isolated in 71–97% yield.

Practical Asymmetric Synthesis of a Potent PDE4 Inhibitor via Stereoselective Enolate Alkylation of a Chiral Aryl−Heteroaryl Secondary Tosylate

A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.

Screening yeasts for the stereoselective reduction of oxoester clofibrate analogues

Reduction of oxoesters 1b– d and 1f, g in the presence of different yeast strains ( Saccharomyces cerevisiae DSM 11285, S. cerevisiae CBS 7336, Cryptococcus curvatus ATCC 20509, Candida bombicola ATCC 22214, Trigonopsis variabilis DSM 70714, Kluyveromyces marxianus CBS 6556) affords hydroxy esters 2b– d and 2f, g with diastereoisomeric excesses (de) up to >99%. Hydrolytic enzyme(s) contained in the yeasts catalyzed to some extent the hydrolysis of the oxoesters to the corresponding acids, which undergo decarboxylation followed by reduction of the carbonyl moiety.

Synthesis, pharmacological activity and hydrolytic behavior of glyceride prodrugs of ibuprofen

For reducing the gastrointestinal toxicity associated with ibuprofen its carboxylic group was condensed with the hydroxyl group of 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate to give the ester prodrugs 3a and 3b. The release of ibuprofen from these prodrugs has been studied at pH 3, 4, 5 and 7.4 by HPLC using methanol and 0.05% phosphoric acid (80%) (70:30) as mobile phase. The prodrugs showed insignificant hydrolysis at pH 5 compared to pH 7.4 indicating that the prodrugs do not break in stomach but release ibuprofen at pH 7.4 in adequate amounts. In vivo hydrolysis studies in rats, the peak plasma concentration of ibuprofen was attained in 1.5 h in case of ibuprofen and in 2 h in prodrugs treated animals. The plasma concentration was found to be less at all times in animals treated with ibuprofen compared to the prodrugs treated animals. The maximum anti-inflammatory activity of ibuprofen was observed at 2 h whereas prodrugs showed maximum activity at 3 h and remained practically constant upto 8 h whereas a decrease in activity was observed with free ibuprofen. Further the prodrugs showed less gastric ulcers compared to ibuprofen. An average score of 0.16, 0.45, 0.97 and 0.20, 0.76, 1.02 of ulcers was observed with 3a and 3b compared to an average score of 0.75, 1.10, and 2.97 with ibuprofen. These prodrugs also showed significant protection against acetic acid induced writhings in rats. These finding suggested that both the prodrugs are better in action as compared to the parent drug and are advantageous in having less gastrointestinal side effects.

Synthesis of 2‐phosphinoxidomethyl‐ and 2‐phosphonomethyl glutaric acid derivatives

AbstractMichael addition of the corresponding anions derived from diphenylphosphine oxide, dialkylphosphites, and a cyclic phosphite to α‐methylene‐glutaric esters (1) afforded the title compounds (2–6). Double debenzylation of 2‐phosphono glutaric esters 4b and 5a by catalytic hydrogenation under the appropriate conditions gave the correspon‐ ding diacides 8 and 9, respectively. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:562–565, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20142