Highly efficient synthesis of enantiomerically enriched 2-hydroxymethylaziridines by enzymatic desymmetrization

Both enantiomers of protected and unprotected 2-hydroxymethylaziridines are efficiently and enantiospecifically synthesized by using a combination of enzymatic and synthetic methods. PPL was used for lipase-catalyzed desymmetrization of N-protected serinol. [reaction: see text].     

An efficient synthesis of (R)-3-hydroxytetradecanoic acid

A short, efficient synthesis of (R)-3-hydroxytetradecanoic acid, a key component of bacterial endotoxins, using (R)-oxirane acetic acid ethyl ester as the source of chirality is described. The method is general and can be used in the preparation of other chiral 3-hydroxy acids.     

Highly efficient synthesis of 5-benzyl-3-aminoindazoles

A rapid and efficient procedure for the preparation of 5-benzyl-3-aminoindazoles 1 is reported. Key intermediates are fluoro-cyano diarylmethanes 2 which have been obtained by two different synthetic approaches. Benefits of these methods result from the use of commercially available starting materials and practical experimental conditions that allow easy scale-up.     

Simultaneous enzymatic synthesis of (S)-3-fluoroalanine and (R)-3-fluorolactic acid

A coupled enzymatic system for the simultaneous synthesis of (S)-3-fluoroalanine (1a) and (R)-3-fluorolactic acid (3) with l-alanine dehydrogenase (l-AlaDH) from Bacillus subtilis and rabbit muscle l-lactate dehydrogenase (l-LDH) using rac-1 and NAD⁺ is described. Analysis of isolated products of the laboratory preparative scale process revealed 1a in 60% yield and 88% ee and 3 in 80% yield and over 99% ee. The compounds 1a and 3 represent chiral building blocks for the synthesis of several products with pharmacological activity.     

Highly efficient synthesis of ketoheptoses

A reliable, facile, high overall yielding and diastereoselective synthesis of ketoheptoses was developed and applied for preparation of the two most diabetogenic ketoheptoses as well as in a modified version for the synthesis of kamusol.     

Highly efficient synthesis of trimethylarsine

A convenient, highly efficient, and environmentally safe procedure for the preparation of trimethylarsine was proposed. A quantitative yield of this compound in the reaction of As₂O₃ with AIMe₃ was attained for the first time by using mechanochemical activation of the process.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2122–2123, August, 1996.     

Highly efficient and metal-free synthesis of tri- and tetrasubstituted imidazole catalyzed by 3-picolinic acid

3-Picolinic acid is an efficient organo-catalyst for a one-pot three-component synthesis of 2,4,5-triaryl substituted imidazole. Moreover, the utility of this catalyst has been extended to the four-component synthesis of 1,2,4,5-tetra-substituted imidazole. The pivotal advantages of this process are easy purification, cost-effectiveness, and high yielding, above all environmentally benign protocol.     

Highly efficient synthesis of fused bicyclic 2,3-diaryl-pyrimidin-4(3H)-ones via Lewis acid assisted cyclization reaction

An expedient one-pot synthesis of fused bicyclic 2,3-diaryl-pyrimidin-4(3H)-ones from three readily available components is described. The key step is a Lewis acid assisted cyclization reaction.     

Highly efficient synthesis of chiral beta-amino acid derivatives via asymmetric hydrogenation

The Rh-TangPhos complex is an efficient hydrogenation catalyst for making chiral beta-amino acid derivatives. With the Rh-TangPhos system, high enantioselectivities (up to 99.6%) and turnover numbers have been obtained in the hydrogenation of E/Z isomeric mixtures of both beta-alkyl and beta-aryl beta-(acylamino)acrylates. [reaction: see text]     

Highly efficient two-step synthesis of C-sp3-centered geminal diiodides

[reaction: see text] Trisubstituted gem-diiodoalkenes of functionalized chains are efficiently reduced to the corresponding terminal geminal diiodides in high yields upon treatment with the diazene precursor, diethyl 4-(hydrazinosulfonyl)-benzyl phosphonate.     

Highly efficient and green synthesis of diacylphloroglucinol over treated natural zeolite mordenite and the optimization using response surface method (RSM)

Herein, we report a greener and highly efficient route for the Friedel-Craft acylation of phloroglucinol over Indonesian treated natural zeolite mordenite (nHZMOR) catalyst to provide value-added diacylphloroglucinol derivatives under solvent-free conditions. The nHZMOR showed a high catalytic performance in Friedel-Craft acylation of a phloroglucinol reaction, and diacylphloroglucinol derivatives were obtained in excellent yields. The advantages of the use of this catalyst are solvent-free, shorter reaction time, high yields, and its recyclable ability. Easy catalyst separation was demonstrated through filtration and reused several times without noticeably decreasing its catalytic activity; however, with regeneration treatment, its catalytic performance can be improved. The effect of catalyst loading, reaction temperature, solvent effect and reaction time has been extensively studied. In addition, the chemical process was enhanced by the use of coupling automated synthesis equipment with the Response Surface Method (RSM) to optimize the Friedel-Craft acylation reaction. Also, a reasonable reaction mechanism had presented.     

Highly efficient one-pot synthesis of tetrahydropyridines

The combination of aromatic aldehydes, and 1,3-dicarbonyl compounds in the presence of a catalytic amount of poly(N,N′-dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] and N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide [TBBDA] leads to the formation of highly substituted tetrahydropyridines. In this way, a series of pharmacologically interesting substituted piperidine derivatives were obtained in moderate to high yields at room temperature.     

H-Y-zeolites induced heterocyclization： Highly efficient synthesis of substituted-quinazolin-4（3H）ones under microwave irradiation

A highly efficient synthesis of 2-amino-N-substituted-benzamides was performed by the condensation of isatoic anhydride with several amines in solvent-free conditions under microwave irradiation. H-Y-zeolites induced heterocyclization of these products with ortho-esters under similar conditions afforded the relevant substituted-quinazolin-4(3H)ones in high yields.     

Novel, efficient total synthesis of natural 20(S)-camptothecin

Enantiopure 20(S)-camptothecin has been prepared from a known hydroxypyridone through a novel approach that involves a Claisen rearrangement, an asymmetric nucleophilic ethylation, a Heck coupling and a Friedl?nder condensation as the key transformations.     

New, efficient synthesis of oseltamivir phosphate (Tamiflu) via enzymatic desymmetrization of a meso-1,3-cyclohexanedicarboxylic acid diester

A new, enantioselective synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate 1 (Tamiflu) and its enantiomer ent-1 starting from cheap, commercially available 2,6-dimethoxyphenol 10 is described. The main features of this approach comprise the cis-hydrogenation of 5-(1-ethyl-propoxy)-4,6-dimethoxy-isophthalic acid diethyl ester (6a) and the desymmetrization of the resultant all-cis meso-diesters 7a and 7b, respectively. Enzymatic hydrolysis of the meso-diester 7b with pig liver esterase afforded the (S)-monoacid 8b, which was converted into cyclohexenol 17 via a Curtius degradation and a base-catalyzed decarboxylative elimination of the Boc-protected oxazolidinone 14. Introduction of the second amino function via S(N)2 substitution of the corresponding triflate 18 with NaN3 followed by azide reduction, N-acetylation, and Boc-deprotection gave oseltamivir phosphate 1 in a total of 10 steps and an overall yield of approximately 30%. The enantiomer ent-1 was similarly obtained via an enzymatic desymmetrization of meso-diester 7a with Aspergillus oryzae lipase, providing the (R)-monoacid ent-8a.     

Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.     

Highly efficient synthesis of O-(2,4-dinitrophenyl)hydroxylamine. Application to the synthesis of substituted N-benzoyliminopyridinium ylides

An efficient two-step synthesis of O-(2,4-dinitrophenyl)hydroxylamine is described along with a comparison of its aminating efficiency with O-mesitylenesulfonylhydroxylamine (MSH). It was used in an expedient N-amination/benzoylation procedure involving various substituted pyridines, leading to polysubstituted N-benzoyliminopyridinium ylides, and the scope of its amination power was studied.     

An efficient enantioselective synthesis of (S)-(-)-acromelobic acid

[reaction: see text] A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF(4) catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.     

Highly efficient synthesis of beta-amino acid derivatives via asymmetric hydrogenation of unprotected enamines

A direct asymmetric hydrogenation of unprotected enamino esters and amides is described. Catalyzed by Rh complexes with Josiphos-type chiral ligands, this method gives beta-amino esters and amides in high yield and high ee (93-97% ee). No acyl protection/deprotection is required.     

Highly efficient and stereoselective synthesis of beta-glycolipids

beta-Galactosylceramide and glycolipid analogues were prepared in high yield and with complete chemo and stereoselectivity by reaction of alpha-iodo glycosides with stannyl ceramides, formed in situ. TBAI was used to activate both the iodogalactose and the stannyl ether.