An Efficient Synthesis of Selective Human NR2A Antagonist NVP-AAM077

A short and efficient synthesis of the selective human N-methyl-D-aspartate （NMDA） receptor 2A （NR2A） antagonist NVP-AAM077 is described. The target was achieved in 8 steps and in 54% overall yield from the commercially available chemical 3-methylbenzene-1,2-diamine. A NaIO4/DMF-based oxidation of the bromide to corresponding aldehyde and an addition of phosphinic acid ester to the aldimine successfully served as the key steps.     

An Improved Synthesis of Retinoic Acid from β-Ionone

A convenient and large-scale preparation of retinoic acid 1 from β-ionone in five steps with 38% overall yield is described.The key steps are the epoxidization of 2 with a new methylated agent and the condensation 4 with tetraethyl methylenediphophonate in one-pot procedure to prepare 6.     

Synthesis,Crystal Structure and Biological Evaluation of 4-Chloro-2-(morpholine-4-carbonyl)phenyl-4′-methoxybenzoate as Molluscicidal Agent

The title compound 4-chloro-2-(morpholine-4-carbonyl)phenyl-4'-methoxybenzoate(C19H18ClNO5, Mr = 375.79), a 5-chlorosalicylic acid derivative incorporating morpholine moiety, was conveniently synthesized through two steps and crystallized in the monoclinic space group P21/c with a = 7.8501(10), b = 9.3149(12), c = 25.133(3), V = 1836.2(4)3, Z = 4, Dc = 1.359 Mg/m3, λ = 0.71073, μ(MoKα) = 0.237 mm-1, F(000) = 784, R = 0.0447 and wR = 0.1227 for 3982 independent reflections with I 2σ(I). The dihedral angles formed between 4-methoxybenzene and 5-chlorobenzene rings, the 5-chlorobenzene and morpholine, and 4-methoxybenzene and morpholine rings are 82.55(3), 72.56(5) and 47.68(0)° by X-ray analysis, respectively. Bioassay shows that the title compound has a good molluscidal effect.     

Isolation and Crystal Structure of 1',4'-Trans-diol of Abscisic Acid

1 INTRODUCTION It has been reported that botrytis cinerea, a plant pathogenic fungus, can produce abscisic acid ((2- cis,4-trans)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-2- cyclohexen-1-yl)-3-methyl-2,4-pentadienoic acid 1)[1] and 1?,4?-trans-diol of abscisic acid 2 that is a pre- cursor of 1[2]. Abscisic acid is an important plant hormone that can inhibit the germination of seeds[3]. Meanwhile, the derivatives of 2, 1?,4?-trans-diol of abscisic acid ester 3 and 4?-methoxy derivative 4, are oil…     

Synthesis,Mass Spectrometric Studies,and Biological Evaluation of 3,5-Dimethoxyhomophthalic Acid and Related Compounds

3,5-Dimethoxyhomophthalic acid was synthesized in four steps from 3,5-dimethoxycinnamic acid via a series of reactions including cyclization of 3-(3',5'-dimethoxyphenyl)propionic acid to 5,7-dimethoxy-1-indanone and oxidative decomposition of methyl-2-hydroxy-2-[5,7-dimethyoxy-1-oxo-1H-inden-2(3H)-ylidene]acetate to 3,5-dimethoxyhomophthalic acid.The synthesized compounds were characterized by elemental analysis,IR,1H NMR,and MS.The biological evaluation experiments of 3,5-dimthoxyhomophthalic acid and the related synthesized compounds were also carried out.Naturally occurring biologically active isocoumarins were prepared in a single step by the condensation of the homophthalic acid with appropriate acid chlorides.     

The Studies of the Reactions of 2, 4, 6-Triphenylpyrylium Tetrafluoroborate with Amino Acids

The reactions of triphenylpyrylium salt 1 with various amino acids were explored and compared. The reactions with most α-amino acids yielded decarboxylation products 2 viadecarboxylation. The reactions with glutamic acid, lysine and ACC (1-aminocyclopropyl-carboxylic acid) gave triphenylpyridine 8, dimer 9 and acid 5a-ace, respectively. The reactionswith β and γ-amino acids yielded triphenylpyridine by intramolecular elimination.     

Direct Synthesis of Acetic Acid from CH4 and CO2 in the Presence of O2 over a V2O5-PdCl2／Al2O3 Catalyst

The possibility of synthesizing acetic acid from CH4 and CO2 in the presence of O2 over a V2O5-PdCl2/Al2O3 catalyst has been explored. The result shows that it is feasible in catalyzing a direct conversion of CH4, CO2 and O2 to acetic acid. It is concluded that both CO2 and O2 are involved in the formation of acetic acid.     

Synthesis and Crystal Structure of N-Hydroxy-9-(3’,4’-methylene- dioxyphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9, 10-decahydroacridine in Aqueous Media

1 INTRODUCTION Acridine derivatives are described to have many applications, such as biological fluorescent probes[1] as well as anti-tumor[2], anti-bacterial[3], anti-HIV[4] and anti-malarial[5] agents. Because of the importance of acridine derivatives, much work has been done for several decades. Among them the classical synthetic methods involve condensing functionalized anilines and o-halogeno- benzoic acid derivatives as well as several other steps resulting in the desired acridine[…     

Synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2- ethanediol and 1-[6-Fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]- (1R)-1,2-ethanediol

Benzopyran compounds possess diverse pharmacological properties such as β-blockade, anticonvulsant and antimicrobial.[1,2] Our interest has been focused on the synthesis of 1-[6-Fluoro-2S]-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (6) and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (7) which are particularly convenient precursor to (S,R,R,R)-NE (8). 8 containing four asymmetrical carbon atoms was reported to be the most active isomer.[3] Chandrasekhar[4] has reported on the synthesis of 8. The key step to synthesize this compound is to obtain the chiral chromanone 6 and 7. 6 was accomplished in 8 steps by the Clasien rearrangement and a one-pot Sharpless asymmetric epoxidation, but the compound 7 was accomplished in 10 steps. Johannes[5] used Zr-catalytic kinetic resolution of allylic ethers and Mo-catalyzed chromene formation to synthesize 8 in 14 steps. However both of the methods request many synthetic steps and expensive reagents.     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Synthesis of fully protected (2R,3R,4S)-4-amino-7-guanidino-2,3-dihydroxy heptanoic acid

(2R,3R,4S)-4-Amino-7-guanidino-2,3-dihydroxyheptanoic acid (AGDHE), a common constituent of biologically active marine peptides, callipeltin A (1) and neamphamide A, was synthesized as its orthogonally protected derivative from l-glutamic acid in 15 steps. Guanidination by the Mitsunobu condition and osmium-catalyzed dihydroxylation of the corresponding Z-olefin were employed as the key steps.     

Synthesis of methyl N-Boc-(2S,4R)-4-methylpipecolate

An efficient stereoselective synthesis of fully protected (2S,4R)-4-methylpipecolic acid has been developed. The synthesis was achieved by initial asymmetric α-alkylation of glycine with a chiral iodide, affording the linear precursor as a single stereoisomer. Subsequent aldehyde formation using OsO(4)/NaIO(4) followed by immediate intramolecular cyclization afforded an enamine that was then subjected to hydrogenation to give the final compound in 23% yield over 10 steps.     

Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides

Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides.     

Synthesis of 2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid, an important intermediate of rosmarinic acid biosynthesis.

A simple method to synthesize (+/-)-2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid (1), a key intermediate in rosmarinic acid biosynthesis in higher plant cells, was established by condensation of protected 4-coumaric acid and (+/-)-3-(4-hydroxyphenyl)lactic acid followed by deprotection. A stable supply of 1 thus attained will lead to biochemical and molecular biological characterization of later steps of rosmarinic acid biosynthesis.     

Selective synthesis of epolactaene featuring efficient construction of methyl (Z)-2-iodo-2-butenoate and (2R,3S,4S)-2-trimethylsilyl-2,3-epoxy-4-methyl- gamma-butyrolactone

[reaction: see text] (+)-Epolactaene was synthesized in 14 steps in the longest linear sequence. The synthesis is highlighted by a highly efficient preparation of the lactone intermediate 4, which only requires three steps from the commercially available (S)-3-butyn-2-ol. It also features a fully stereocontrolled synthesis of the intermediate 9, which was constructed through the use of Zr-catalyzed methylalumination of alkynes and a series of Pd-catalyzed organozinc cross-coupling reactions, such as homopropargylation, direct ethynylation, and alkenylation of the methyl ester of (Z)-alpha-iodocrotonic acid (3).     

A concise synthesis of protected (2S,4R)-4-hydroxyornithine

A short synthesis of the nonproteinogenic amino acid, (2S,4R)-4-hydroxyornithine is described. Starting from racemic benzyl glycidol, the scaffold of the target compound was constructed in high enantio- and diastereoselectivity using Jacobsen’s hydrolytic kinetic resolution (HKR) and regioselective opening of an epoxide as key steps.     

Synthesis of Cyclosporine. I. Synthesis of enantiomerically pure (2S,3R,4R,6E)-3-hydroxy -4-methyl-2-methylamino-6-octenoic acid starting from tartaric acid

Starting from R,R-(+)-tartaric acid, the synthesis of (2S,3R,4R6E)-3-hydroxy -4-methyl-2-methylamino-6-octenoic acid in 24 steps is reported. This novel amino acid is found in the cyclic undecapeptide cyclosporin A, isolated from the fungal strain Tolypocladium inflatum GAMS . Its stereospecific synthesis allowed, for the first time, the isolation and characterization of the new amino acid previously reported as the ‘C-9-amino acid’ [1].     

Synthesis of 2-propyloxazole and 2-propyloxazole-4-carboxylic acid derivatives

2-Propyloxazole (VI) was obtained in a number of steps starting from butyronit rile. The hydrazide and amide were obtained from ethyl 2-propyloxazole-4-carboxylate; the amide was converted to the nitrile, from which the thioamide and amidoxime were obtained by the usual method. Attempts to convert VI to 2-propylisonicotinic acid or its nitrile by the reaction of VI with acrylic acid or acrylonitrile did not give positive results.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 7–9, January, 1972.     

Synthesis, structure and reactivity of 1-(4-nitrobenzyl)-2-chloromethyl benzimidazole

The synthesis of 1-(4-nitrobenzyl)-2-chloromethyl benzimidazole, which undergoes a nucleophilic substitution with pyridine in the absence of additional base, is reported. The key steps are the reaction of 1,2-phenylenediamine to give exclusively the mono-substituted product and the avoidance of minor by-products via the use of glycolic acid for the cyclisation step. The X-ray structures of 1-(4-nitrobenzyl)-2-chloromethyl benzimidazolium chloride and 1-[1-(4-nitrobenzyl)benzimidazol-2-ylmethyl]pyridinium chloride are presented.     

4-Ferrocenyl-2-fluorophenylboronic acid: synthesis and structure

Russian Chemical Bulletin - 4-Ferrocenyl-2-fluorophenylboronic acid was obtained from ferrocene in two steps. In crystal, this compound forms a dimer due to the O–H...O hydrogen bonds and...