Acid 1b Research Articles

Synthesis of New Optically Active and Racemic Phenylsuccinamic Acids

The synthesis, isolation, and characterization of new (S)-(+)- and racemic phenylsuccinamic acids, obtained from the reaction of (S)-(+)-phenylsuccinic anhydride (1) with five different primary amines (2a-e) is described.Ring opening of anhydride 1 led to the formation of two isomeric phenylsuccinamic acid products with the phenyl substituent β to the amide function being the preferred product. Complete racemization occurred with all of the α-phenylsuccinamic acids (3a-e) and β-phenylsuccinamic acids 4b and 4c. However, β-phenylsuccinamic acids 4a, 4d, and 4e were found to be optically active.

New (diphenylphosphane)benzoic acid copper(I) derivatives of “scorpionate” ligands with superoxide scavenging activity

New copper(I) complexes have been synthesized from the reaction of CuCl with 4- or 2-(diphenylphosphane)benzoic acid and KH 2B(btz) 2, KHB(btz) 3, NaTp Me, KpzTp, KpzTp Me and KH 2B(im) 2(dmac). The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR ( 1H and 31P{ 1H}) and electrospray mass spectroscopy in solution. Chemiluminescence technique was used to evaluate the superoxide scavenging activity of these new copper complexes.

Synthesis of the 8‐Hydroxy Acid of Jasplakinolide

AbstractThe protected ω‐hydroxy acid 4b contained in the depsipeptide jasplakinolide (1) was prepared in a sequence of 13 steps from the silylated 3‐hydroxy ester 6. By chain extension 6 was converted to the allyl alcohol 10. A subsequent asymmetric cyclopropanation of the allylic alcohol 10 using the Charette method provided the hydroxymethylcyclopropane 12 with excellent diastereoselectivity. This cyclopropanation was used to establish the methyl‐bearing stereocenter at C‐6 of the hydroxy acid 4 by reductive ring cleavage of the (iodomethyl)cyclopropane 14. The alkene 15 was used for a cross alkene metathesis reaction with 2‐methylacrylate 20 providing the enoate 19. The derived allylic iodide 24 served as an electrophile in the final Evans alkylation step to give the ω‐hydroxy acid derivative 26.

Pseudodimorphism of the Trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic Acid Clathrates with Acetic and Propionic Acids

The versatile host compound trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid (1) forms under ambient conditions isostructural complexes with acetic and propionic acids being true clathrates without host-guest type H-bonds. A new modification of the clathrate between 1 and acetic acid (1a) is obtained at sub-room temperature (5 °C) while for preparation of the new crystal form of the clathrate with propionic acid (1b) crystallization temperature should be increased up to 50 °C. Crystal structures of the pseudodimorphs show that homo carboxylic acid dimers existing in the conventional phases are also observed here, demonstrating the new compounds to be of same clathrate type. Crystal data: for 1a: triclinic P-1, a = 8.626(2) A, b = 9.073(2) A, c = 12.042(2) A, α = 76.34(3)°, β = 77.41(3)°, γ = 84.13(3)°, V = 892.5(4) A3, Z = 2, R = 0.0446 for 3171 reflections; for 1b: monoclinic C2/c, a = 13.268(3) A, b = 12.636(3) A, c = 21.786(4) A, β = 90.56(3)°, V = 3652.3(14) A3, Z = 8, R = 0.0618 for 2365 reflections.

Versatility in stabilization of crystalline inclusion complexes of a bulky diol host by various closely related acidic and ester guests

In order to stabilize carboxylic acid and ester molecules in a monomeric state for spectroscopic investigation, solid inclusion formation experiments have been carried out with the 2,2′-bis(hydroxydiphenylmethyl)-1,1′-biphenyl host molecule (1) and various carboxylic acid and ester compounds (27 different species). The IR spectra of the included guest molecules have been registered, and single crystals of five selected complexes (1a–e), containing formic acid (1a), acetic acid (1b), propionic acid (1c), butanoic acid (1d), and ethyl acetate (1e) as guest component, respectively, have been studied by X-ray diffraction. The IR spectroscopic investigations yielded some unexpected νCO absorption frequencies for two of the guest molecules, namely acetic and propionic acids, but not for the other, closely related guest acid or ester molecules in this study. The X-ray diffraction analyses showed the diol host 1 molecule to assemble into similar hexamer associates in all studied crystals, with various acid/ester guests and some water molecules being included in uniform cyclic cavities inside the hexa-host units. Hence, the five solid inclusion compounds have analogous crystal shapes, unit cell dimensions and crystallographic symmetries, and their host frameworks exhibit a high degree of isostructurality. In spite of the pronounced similarities, the X-ray structural study also indicated remarkable differences in the way the various guest molecules stabilize the respective crystal structures, thus giving a possible explanation for the observed IR absorption anomalies.

Synthesis of Optically Active Tetrahydro-3-benzazepine-2-carboxylic Acid Derivatives via the Ring Expansion Reaction of Isoquinolines and Enzymatic Resolution

The facial approach to 3-benzazepine-2-carboxylic acid derivatives (1) via the ring expansion reactions of 10b-hydroxymethyloxazoloisoquinolines (3) to 3-benzazepines (2) is described. Utilizing enzymatic resolution, the synthesis of (-)-(S)-N-Cbz-3-benzazepine-2-carboxylic acid (1b) was achieved.

Synthesis of labelled dihydroartemisinic acid

[15- 13C 2H 3]-Dihydroartemisinic acid ( 2a ), [15-C 2H 3]-dihydroartemisinic acid ( 2b ) and [15- 13CH 3]-dihydroartemisinic acid ( 2c ) have been obtained in good yield and high isotopic enrichment by a reconstructive synthesis from artemisinin. These labelled compounds were designed to be used in biosynthetic experiments to determine the origins of artemisinin and other sesquiterpene natural products from Artemisia annua.

In vivo transformations of dihydroartemisinic acid in Artemisia annua plants

[15- 13C 2H 3]-dihydroartemisinic acid ( 2a ) and [15-C 2H 3]-dihydroartemisinic acid ( 2b ) have been fed via the root to intact Artemisia annua plants and their transformations studied in vivo by one-dimensional 2H NMR spectroscopy and two-dimensional 13C– 2H correlation NMR spectroscopy ( 13C– 2H COSY). Labelled dihydroartemisinic acid was transformed into 16 12-carboxy-amorphane and cadinane sesquiterpenes within a few days in the aerial parts of A. annua, although transformations in the root were much slower and more limited. Fifteen of these 16 metabolites have been reported previously as natural products from A. annua. Evidence is presented that the first step in the transformation of dihydroartemisinic acid in vivo is the formation of allylic hydroperoxides by the reaction of molecular oxygen with the Δ 4,5-double bond in this compound. The origin of all 16 secondary metabolites might then be explained by the known further reactions of such hydroperoxides. The qualitative pattern for the transformations of dihydroartemisinic acid in vivo was essentially unaltered when a comparison was made between plants, which had been kept alive and plants which were allowed to die after feeding of the labelled precursor. This, coupled with the observation that the pattern of transformations of 2 in vivo demonstrated very close parallels with the spontaneous autoxidation chemistry for 2 , which we have recently demonstrated in vitro, has lead us to conclude that the main ‘metabolic route’ for dihydroartemisinic acid in A. annua involves its spontaneous autoxidation and the subsequent spontaneous reactions of allylic hydroperoxides which are derived from 2 . There may be no need to invoke the participation of enzymes in any of the later biogenetic steps leading to all 16 of the labelled 11,13-dihydro-amorphane sesquiterpenes which are found in A. annua as natural products.

Electrochemical Sulfonylation of 4‐tert‐Butylcatechol.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selectivities in Reactions of Organolithium Reagents with Unprotected 2-Halobenzoic Acids

[reaction: see text] Exposing 2-fluorobenzoic acid (1a) to 2.2 equiv of LTMP at ca. -78 degrees C leads to deprotonation at the 3-position whereas 2-chloro/bromobenzoic acids (1b,c) are lithiated adjacent to the carboxylate. The resulting dianions 3Li-1a and 6Li-1b,c are trapped as such by chlorotrimethylsilane. In the absence of internal quench, 6Li-1b,c isomerize to the more stable 3Li-1b,c. The latter eliminate lithium halide and set free benzyne-3-carboxylate (2) that reacts regioselectively with LTMP to give 3-tetramethylpiperidinobenzoic acid (3).

Derivatives of 5‐Oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic Acid: A Tricyclic System Useful for the Synthesis of Potential Intercalators.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Functionalized Pyridylboronic Acids and Their Suzuki Cross‐Coupling Reactions to Yield Novel Heteroarylpyridines.

2-Bromo-5-pyridylboronic acid 2a, 2-chloro-5-pyridylboronic acid 2b, 2-methoxy-5-pyridylboronic acid 2c, and 5-chloro-2-methoxy-4-pyridylboronic acid 4 have been synthesized and shown to undergo palladium-catalyzed cross-coupling reactions with heteroaryl bromides to yield novel heteroarylpyridine derivatives. The X-ray crystal structures of 2a and 2b have been obtained.

Chemospecificity in Arylations of δ‐ and γ‐Ketocarboxylic Acids with P2O5—MsOH, TfOH, and Related Acidic Media.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Electrochemical Sulfonylation of 4-tert-Butylcatechol

Electrochemical oxidation of 4-tert-butylcatechol (1) has been studied in the presence of benzenesulfinic acids (2a and 2b) as nucleophiles in aqueous solution, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinone derived from 4-tert-butylcatechol (1) participates in Michael addition reaction with 2 of form the corresponding arylsulfonylbenzenediols (3a and 3b). The electrochemical synthesis of 3a and 3b has been successfully performed at carbon rod electrodoes in an undivided cell in good yield and purity.

Two chromone-secoiridoid glycosides and three indole alkaloid glycosides from Neonauclea sessilifolia

From the dried roots of Neonauclea sessilifolia, two new chromone-secoiridoid glycosides, sessilifoside and 7″- O-β- d-glucopyranosylsessilifoside, and three novel indole alkaloid glycosides, neonaucleosides A, B, and C, were isolated along with the main known glycosides, 5-hydroxy-2-methylchromone-7- O-β- d-apiofuranosyl-(1→6)-β- d-glucopyranoside, sweroside, loganin, grandifloroside, and quinovic acid 3β- O-β- d-quinovopyranoside-28- O-β- d-glucopyranoside. The structures of these new glycosides were determined by spectroscopic and chemical means. Neonaucleoside A and its C-3 epimer were prepared from secologanin and tryptamine.

A Convenient Synthesis of 2‐Alkyl‐8‐quinoline Carboxylic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Derivatives of 5‐Oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid: A tricyclic system useful for the synthesis of potential intercalators

AbstractThe synthesis of a new series of 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxamides 4a‐i and N1,N2‐Bis(5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐benzoyl)ethylenediamine (5) is reported starting from 2‐chloro‐3‐nitropyri‐dine. Fundamental steps of the synthetic pathway are i) preparation of 2‐(3‐nitro‐pyridin‐2‐ylamino)benzoic acid (1) via copper‐catalyzed condensation of 2‐chloro‐3‐nitropyridine with o‐anthranilic acid, ii) intramolecular cyclization of the acid 1 to 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid (2b) upon treatment with concentrated sulfuric acid and oleum and iii) conversion of the acid 2 to the desired amides 4a‐i and 5. Compounds 4a‐i and 5 are oxygenated azaanalogs of phenazines, a wellknown series of intercalators with cytotoxic activity.

Functionalized pyridylboronic acids and their Suzuki cross-coupling reactions to yield novel heteroarylpyridines.

2-Bromo-5-pyridylboronic acid 2a, 2-chloro-5-pyridylboronic acid 2b, 2-methoxy-5-pyridylboronic acid 2c, and 5-chloro-2-methoxy-4-pyridylboronic acid 4 have been synthesized and shown to undergo palladium-catalyzed cross-coupling reactions with heteroaryl bromides to yield novel heteroarylpyridine derivatives. The X-ray crystal structures of 2a and 2b have been obtained.

A Convenient Synthesis of the Echinacea-Derived Immunostimulator and HIV-1 Integrase Inhibitor (−)-(2R,3R)-Chicoric Acid

The Echinacea-derived immunostimulator and HIV-1 integrase inhibitor (−)-chicoric acid (=2,3-bis{[3-(3,4-dihydroxyphenyl)-1-oxoprop-2-enyl]oxy}butanedioic acid; 1a) was conveniently prepared via a silane-promoted Pd-mediated chemoselective hydrogenolysis of its perbenzylated derivative 12a, which was generated from an efficient and reliable carbodiimide-mediated coupling reaction between the caffeic acid dibenzyl ether derivative 7 and commercially available (+)-dibenzyl L-tartrate (9a). The other naturally occurring dextrorotatory chicoric acid (1b) can be similarly prepared.

Tetraarylpentaborates, [B(5)O(6)Ar(4)](-) (Ar = C(6)H(4)OMe-4, C(6)H(3)Me(2)-2,6): their formation from the reaction of arylboronic acids with an aryloxorhodium complex, structure, and chemical properties.

The reactions of (4-methoxyphenyl)boronic acid (1a) and of (2,6-dimethylphenyl)boronic acid (1b) with (PMe(3))(3)Rh-(OC(6)H(4)Me-4) (2) in a 5:1 molar ratio result in the formation of cationic rhodium complexes with new tetraarylpentaborates [Rh(PMe(3))(4)](+)[B(5)O(6)Ar(4)](-) (3a, Ar = C(6)H(4)OMe-4; 3b, Ar = C(6)H(3)Me(2)-2,6). The characterization of 3a is as follows: orthorhombic space group P2(1)2(1)2(1), a = 14.7600(5) A, b = 17.1675(5) A, c = 19.8654(5) A; V = 5033.7(3) A(3); Z = 4. The characterization of 3b is as follows: orthorhombic space group Pnma, a = 23.704(6) A, b = 17.254(8) A, c = 13.304(2) A; V = 5441(2) A(3); Z = 4. An intermediate complex, [Rh(PMe(3))(4)](+)[Ph(3)B(3)O(3)(OC(6)H(4)Me-4)](-) (4), was isolated from the reaction of phenylboroxine, (PhBO)(3), with 2. The tetraarylpentaborates smoothly undergo hydrolysis to give [Rh(PMe(3))(4)](+)[B(5)O(6)(OH)(4)](-) (5).