Acid 1b Research Articles

Notes on Activity Tests and Constituents of two Supposed Medicinal Plants from South Africa, Englerophytum magalismontanum and Diospyros lycioides desf. subsp. sericea†

Supposed pharmacological effects of extracts from the title plants could not be substantiated, triterpenes 3β,20-lupandiol (1a), uvaol (2a) and ursolic acid (2b) were isolated from Englerophytum and 19β-lupeol (1b) and 2b from Diospyros.

β‐Loop, γ‐loop, and helical peptide conformations in cyclopeptides containing a steroidal pseudo‐amino acid

AbstractThe steroidal pseudo‐amino acids 3ã‐amino‐5β‐cholan‐24‐oic acid (2a), 12ã‐acetoxy‐3ã‐ammonia‐5β‐cholan‐24‐oic acid (2b), and 7ã,12ã‐diacetoxy‐3ã‐amino‐5β‐cholan‐24‐oic acid (2c) are used as rigid spacers in the backbone of the cyclic peptides cyclo(–2a–Phe‐Phe–)2 (1a), cyclo(–2b–Phe‐Phe–)2 (1b), and cyclo(–2c‐Phe‐Phe–)2 (1c). A homogeneous β‐loop conformation is found in the peptide chains of 1a and 1b, while 1c exists as a mixture of ã‐helical and γ‐loop conformations. The structure and homogeneity of the conformations are established by several NMR techniques and are supported by molecular‐dynamics calculations. The peptide conformations depend on the distance and attraction of the two large and lipophilic steroidal parts of the cyclic molecules.

Photochemistry of 4-Thiothymine Derivatives in the Presence of N-9-Substituted-Adenine Derivatives: Formation of N-6-Formamidopyrimidines.

UV irradiation of aqueous solutions containing either 4-thiothymin-1-ylacetic acid (1b) and adenosine (2a), 4-thiothymidine (1a) and adenin-9-ylacetic acid (2b), or 1b and 2b led to 4,5-diamino-6-formamidopyrimidine (N-6-Fapy-Ade) derivatives as observed after irradiation of a mixture of 1a and 2a (J. Am. Chem. Soc. 1996, 118, 8142-8143). These new observations demonstrate that the replacement of one or both nucleoside sugar residues by a carboxymethyl group does not affect the regioselective course of the photochemical reaction. The thermal decomposition of 3a that resulted from irradiation of 1a in the presence of 2a, was examined along with its behavior under mild alkaline conditions. Finally, irradiation of N-3-methyl-4-thiothymidine (6a) in the presence of adenosine gave the N-3-methylcytidine derivative 7.

Enzymatic Resolution of Chiral 2-Hydroxy Carboxylic Acids by Enantioselective Oxidation with Molecular Oxygen Catalyzed by the Glycolate Oxidase from Spinach (Spinacia oleracea)

The enzymatic oxidation of a variety of saturated and unsaturated aliphatic derivatives of racemic 2-hydroxy acids 1 to their 2-oxo acids 2 with molecular oxygen catalyzed by the glycolate oxidase from spinach (Spinacia oleracea) was shown to proceed highly enantioselectively. Thus, the glycolate oxidase-catalyzed kinetic resolution provides a convenient biocatalytic method for the preparation of enantiomerically pure (R)-2-hydroxy acids. The absolute configuration of the (R)-2-hydroxy acid 1b was assigned by comparison of the measured optical rotation value with that of the literature data and by application of the exciton-coupled circular dichroism method (ECCD) on its bichromophoric 2-naphthoate 9-methylanthryl derivative 3b. These results establish the ECCD method as a convenient microscale chirooptic tool for the configurational assignment of 2-hydroxy acids.

27‐Ald‐triterpenoid saponins from Adina rubella

AbstractFour new triterpenoid saponins were isolated from the roots of Adina rubella Hance. They were characterized as adinaic acid 3β‐[α‐L‐rhamnopyranosyl(1→2)‐β‐D‐glucopyranosyl(1→2)‐β‐D‐glucurono‐pyranoside‐6‐O‐methyl ester]‐2‐O‐β‐D‐glucopyranoside, adinaic acid 3β‐O‐[a‐L‐rhamnopyranosyl(1→2)‐β‐D‐glucopyranosyl(1→2)‐β‐D‐glucuronopyranosid‐6‐O‐butyl ester]‐28‐O‐β‐D‐glu‐copyranoside, adinaic acid 3β‐O‐[β‐D‐glucopyranosyl(1→2)‐β‐D‐glucopyranosyl]‐(28→ l)‐β‐D‐glucopyranosyl(1→6)‐β‐D‐glucopyranosyl ester, 27‐hydroxyursolic acid 3β‐O‐[α‐L‐rhamnopyranosyl (1→ 2)‐β‐D‐glucopyranosyl(1→2)‐β‐D‐glucuronopyranoside‐6‐O‐methyl ester]‐28‐O‐β‐D‐glucopyranoside. Their structures wen elucidated by spectral methods, specially with the aid of 2D NMR techniques. Their complete assignments of the 1H and 13C NMR signals were carried out.

Synthesis of a Novel C60-Containing Polyimide: A New ‘Charm-Bracelet’ Type of Polyimide and Copolyimide

The fullerene-containing polyimides were synthesized by the reaction of diamines and C60-containing dianhydride 2 and copolyimides were synthesized by the reaction of 2, 4, 4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 4, 4′-diaminodiphenyl ether (ODA). Polyamic acids 3a, b and copolyamic acids 8b–e were soluble in polar aprotic solvents such as DMAc, DMF, DMSO and NMP, whereas 8b–e showed additional solubility in THF. The molecular weights of polyamic acids 3a, b and copolyimides 9b−e determined by gel permeation chromatography were in the range of 1.0 × 10 4−7.8 × 103 and 5 × 104−2.8 × 104 mol g−1, respectively. Polyamic acid 3a ;b contained other lower molecular weight oligomers. TGA results for polyimides and copolyimides showed thermal stability and the 10% weight loss temperatures were in the range of 430–520 °. Distinct glass transition temperatures of C 6′-containing polyimides were not observed by DSC measurement. The cyclic voltammograms of 2 and 3a indicated four reduction waves corresponding to C60 redox reactions, but the polyamic acid 8e showed one reduction wave at −1.39 V.

Chiral 2,2-disubstituted cyclopropanecarboxylic acids: Effective derivatizing agents for analysis of enantiomeric purity of alcohols and for resolution of 1,1′-bi-2-naphthol

The enantiomeric purities of secondary alcohols can be easily analyzed by GC and HPLC through derivatization to the esters of 2,2-disubstituted cyclopropanecarboxylic acids 1, and by 1H NMR analysis of the esters of 2,2-diphenylcyclopropanecarboxylic acid ( 1b). In addition racemic 1,1′-bi-2-naphthol is easily resolved through derivatization to monoesters of 2,2-dimethylcyclopropanecarboxylic acid ( 1a), which are crystallized selectively and sequentially in high yields with high optical purities.

Synthesis, pharmacokinetics, and biological activity of a series of new pyridonecarboxylic acid antibacterial agents bearing a 5‐fluoro‐2‐pyridyl group or a 3‐fluoro‐4‐pyridyl group at N‐1

AbstractThe 1‐(5‐fluoro‐2‐pyridyl) or 1‐(3‐fluoro‐4‐pyridyl) group was introduced in the syntheses of new pyridonecarboxylic acid antibacterial agents. 1‐(5‐Fluoro‐2‐pyridyl)‐6‐fluoro‐1,4‐dihydro‐7‐(4‐methyl‐1‐piperazinyl)‐4‐oxoquinolone‐3‐carboxylic acid 7b (DW‐116) showed a moderate in vitro antibacterial activity but it was found to have very excellent pharmacokinetic profiles so that 7b (DW‐116) showed dramatic increased in vivo efficacy.

Mitsunobu C-Alkylation of Meldrum's Acids

C-Dialkylation of Meldrum's acid (2a) and 5-benzyl Meldrum's acid (2b) can be achieved through Mitsunobu dehydration using allylic and arylmethyl alcohols as alkylating agents. This is the first time that the Mitsunobu reaction is successfully applied to the C-alkylation of a highly enolizable cyclic β-dicarbonyl system. With primary (allylic and arylmethyl) alcohols, the alkylations always take place at the carbon bearing the hydroxy group. For secondary allylic alcohols, a catalytic amount of Pd(0) must be added to enhance the regioselectivity of C-alkylation over O-alkylation. With (Ph3P)4Pd(0) as a catalyst, the reaction occurs specifically at the less hindered carbon, and the configuration of the resultant double bond is always trans. Attempts to monoalkylate Meldrum's acids 2a and 2b failed.

An Enantioselective Synthesis of (-)-Nonactic Acid and (+)-8-epi-Nonactic Acid Using Microbial Reduction

An enantioselective synthesis of (-)-nonactic acid (2a) and (+)-8-epi-nonactic acid (2b) is described. The microbial reduction of the dl-ketone 3 with baker's yeast gave two easily separable diastereomeric alcohols 11a and 11b, each in over 97% ee. These alcohols were converted to 2a and 2b in 4 steps.

Asymmetric synthesis of l-thienylalanines

l-Thienylalanines were prepared via the hydantoin and azlactone routes with the key step consisting of the microbial transamination of 2-hydroxy-3-thienylacrylic with l-aspartic acid as amino donor. The transamination reaction was performed by a genetically engineered E. coli strain on scales up to 100 g of l-3-(2-thienyl)alanine 1a and is also applicable to the preparation of the isomeric amino acid 1b and some ring-substituted derivatives.

Lewis Acid-Driven Accelerated Living Polymerization of Lactones Initiated with Aluminum Porphyrins. Chemoselective Activation of Ester Groups by Lewis Acid

Ring-opening polymerization of δ-valerolactone (δ-VL) initiated with (5,10,15,20-tetraphenylporphinato)aluminum methoxide ((TPP)AlOMe, 1; X = OMe) was dramatically accelerated upon addition of methylaluminum bis(2,6-di-tert-butyl-4-methylphenolate) (2a) and bis(2,4,6-tri-tert-butylphenolate) (2b) via coordinative activation of monomer, but was accompanied by transesterification, resulting in broadening of the polymer molecular weight distribution (MWD) at the later stage of polymerization. On the contrary, when methylaluminum bis(2,6-di-X-phenolate)s (X = Cl (2c), Br (2d), I (2e), and Ph (2f)) were used as Lewis acids, the polymerization proceeded also rapidly, retaining the narrow MWD. 13C NMR studies on the Lewis acid (2b or 2f)−δ-VL and −poly(δ-VL) mixtures showed that the coordination abilities of 2b and 2f toward the monomer ester group are comparable to each other, while 2f shows a lower affinity to the polymer ester group than 2b. 2a was also able to accelerate the polymerization of β-butyrolactone (β-BL) with (TPP)AlOMe or (5,10,15,20-tetraphenylporphinato)aluminum chloride ((TPP)AlCl, 1; X = Cl) to different extents depending on the mode of ring scission, where the MWD of the polymer remained narrow throughout the accelerated polymerization (Mw/Mn = 1.1−1.2).

Enantioconvergent transformation of racemic cis-Dialkyl substituted epoxides to (R,R) threo diols by microsomal epoxide hydrolase catalysed hydrolysis

Both enantiomers of (±)-9,10-epoxystearic acid ( 1b), cis-(±)-5,6-epoxyhexadecane ( 1c) and cis-(±)-11,12-epoxyhexadecan-1-ol ( 1d) as well as the meso cis-9,10-epoxyoctadecane ( 1a) undergo microsomal epoxide hydrolase catalyzed hydration at the (S) carbon to give the corresponding (R,R) threo diols in a >90 e.e.

Structural Assembly of Rigid Hydroxycarboxylic Acid Frameworks - Solid State Structures of Two Substituted 6-Hydroxy-trans-3-hexenoic Acids

5-(1-H ydroxycyclohexyl)-trans -3-pentenoic acid (2a) and 5 -(2 -hydroxy-2 -indanyl)-trans-3-pentenoic acid (2b) both exhibit associated structures in the solid state that contain strictly alternating repetitive -OH / HO2C- hydrogen bonded arrays. The (2a)„ structure is helical, whereas the association of 2b leads to a three dimensional assembly of tube-like (2b)„ structures. In contrast, the related sterically shielded 6,6-diphenyl-6-hydroxy-trans -3-hexenoic acid (2c) exhibits only a conventional carboxylic acid dimer structure in the solid state.

Asymmetrische Elektrophile α‐Amidoalkylierung, 11. Neue chirale Hilfsgruppen aus (+)‐Camphersäure

Asymmetric Electrophilic α‐Amidoalkylation, 11. – New Chiral Auxiliaries from (+)‐Camphoric AcidHerrn Professor Eberhard Reimann mit den besten Wünschen zum 60. Geburtstag gewidmet. The chiral bicyclic carboxylic acids 3b–e have been prepared in a few steps from camphoric acid. They were designed as new chiral auxiliaries for asymmetric synthesis with chiral N‐acyliminium ions featuring precomplexation as a mechanism for asymmetric induction. Their asymmetric induction was evaluated in alkylation reactions with the enamides 5b–e being performed by addition of HCl and subsequent treatment of the resulting α‐chloro amide with AlEt3. The carboxylic acid 3e turned out to be well suited as a chiral auxiliary providing high asymmetric induction (e.g. 92.9/7.1 with ZnEt2) and moderate chemical yields (66% 12e + 13e) and being easily removed by acid hydrolysis without destruction.

Organoalane-mediated isomerization of ascorbic and isoascorbic acid derivatives

Derivatives of l-ascorbic acid 2a, 10a 11a and d-isoascorbic acid 2b, 10b 11b , when treated with triisobutylaluminium, partly epimerize to give the corresponding derivatives of l-isoascorbic acid ent-2b, ent-10b or d-ascorbic acid ent-2a, ent-11a , respectively. Complete removal of the protecting groups is effected by hydrogenolysis of the benzylidene acetals ent-10 and ent-11a. This reaction leads to d-ascorbic acid ent-1a or l-isoascorbic acid ent-1b, respectively. Furthermore, the four acetonides 2 were converted by ozonolysis, transesterification and finally catalytic hydrogenation to the threonic and erythronic acid ketals 9.

Self‐Assembly of Substituted 6‐Hydroxy‐ trans ‐3‐hexenoic Acids – Formation of Extended Ribbon‐Like Structures by Hydrogen Bonds

The substituted 6-hydroxy-trans-3-hexenoic acids 2a and 2b are prepared by an organometallic template reaction involving a sequence of CC coupling reactions between a CO2 equivalent, butadiene, and 3-cyclopenten-1-one or 3,4-diphenyl-3-cyclopenten-1-one, respectively. In the crystal 2a assembles to form an infinite ribbon-type structure, exhibiting an alternating array of 12 and 18 atom-containing loops. The former are each constructed by an alternating CO2H/OH/CO2H/OH sequence, originating from four different monomeric units, that are linked together by means of hydrogen bonds. Two complementary ribbons of 2a are connected by van der Waals interactions to form staples that constitute the microscopic building blocks of the true (2a)n structure in the crystal. Stacks of cyclopentene π bonds are oriented inside the columnar structure of 2a. Acid 2b also forms a related ribbon-like assembly in the solid state. Here the bulky 3,4-diphenylcyclopentadienylidene moieties are oriented laterally at the ribbons, and van-der-Waals interactions with adjacent ribbons construct a three-dimensional hydroxyhexenoic acid network.

The influence of the nature of the solvent on the crystal structure and the character of formation of hydrogen bonds inN?-(5-nitrofurfurylidene)isonicotinehydrazide

N′(5-Nitrofurfurylidene)isonicotinehydrazide (1) was synthesized in the reaction of nicotinic acid hydrazide with 5-nitrofurfurol in anhydrous or aqueous ethanol. Crystals of different shape and color were obtained depending on the conditions of synthesis and the nature of the solvent. As was established by IR spectroscopy, compound1 in the crystalline state forms solvates of various types. An X-ray study of two different crystals, one obtained by recrystallization from methanol (1a), and the other obtained from aqueous acetic acid (1b), was performed. In the crystal structure of1a intermolecular hydrogen bonds (IMHB) of the NH...N(Py) type occur; the crystals1b are built of solvates with one molecule of acetic acid in which the components are bonded by the IMHB (Ac)O-H..N(Py). The solvates are linked in an infinite chain by the amidohydrate IMHB C=O...W...H-N.

An Improved Method for the Preparation OF 3,5-Difluorosalicylaldehyde and 3,5-Difluorosalicylic Acid#

Abstract An improved method for the synthesis of 3,5-difluorosalicylic acid (3b) and 3,5-difluorosalicylaldehyde (3a) is described. 2,4-Difluorophenol (4) undergoes a formylation reaction to afford aldehyde 3a which is oxidized to the desired acid 3b. This method avoids the use of the highly corrosive HF and fluorine gas and requires no special laboratory apparatus. #Dedicated to the memory of Rosemarie R. Ungarelli, Academic Advisor, Chemistry Department, Long Island Univeristy, C.W. Post Center.

Ring closure reactions of azidouracils to oxazolo‐ and isoxazolopyrimidines

AbstractThermolysis of 6‐azidouracils 1 in the presence of polyphosphoric acid leads either to oxazolo[5,4‐d]pyrimidine‐5,7‐diones 5 (by reaction with benzoic acid 2a) or to isoxazolo[3,4‐d]pyrimidine‐4,6‐diones 7 (by reaction with aliphatic carboxylic acids 2b,c). 5‐Benzoylpyrimidinetriones 12 could be shown to cyclize to isoxazolo[5,4‐d]pyrimidine‐4,6‐diones 15 by chlorination with phosphorus pentachloride and subsequent reaction with sodium azide.