First highly stereoselective synthesis of anti-alpha-trifluoromethyl-beta-amino acid derivatives

The Reformatsky-type reaction of 2-bromo-3,3,3-trifluoropropanoic imide with various types of imines, in the presence of ZnBr2 as a Lewis acid in THF at 0 degrees C for 3 h, gave the corresponding alpha-trifluoromethyl-beta-amino acid derivatives in a highly anti-selective manner.     

Microwave-assisted one-step synthesis of fenamic acid hydrazides from the corresponding acids

A facile and efficient method for synthesis of fenamic acid hydrazides from their acids in one-step reaction under microwave irradiation and solvent-free conditions was developed. Compared with the two-step conventional heating method, the process was simple, the reaction time was very short and the yields were almost quantitative.     

Silica sulfuric acid as a highly efficient catalyst for the synthesis of diarylacetic acids

An efficient heterogeneous method for the synthesis of diarylacetic acids was developed utilizing silica sulfuric acid as a catalyst. The reaction is highly efficient with a small amount of catalyst for the combination of a variety of electron-neutral to electron-rich arenes with glyoxylic acid. The reaction can also be utilized to synthesize unsymmetric derivatives from activated mandelic acids in good to excellent yields.     

Divergent and stereoselective synthesis of dafachronic acids

A new divergent synthesis of DAF-12 ligands, namely Δ⁴- and Δ⁷-dafachronic acid, is described starting from the natural bile acid hyodeoxycholic acid. Homologation of the side chain followed by stereoselective reduction of the Δ²⁴ olefinic linkage, 6α-dehydroxylation and C₃-oxidation affords dafachronic acids in good yields and high diastereoselectivity making this approach easily accessible and scalable.     

Oxazolinyloxiranyllithium-mediated stereoselective synthesis of alpha-epoxy-beta-amino acids

[reaction: see text] The stereoselective synthesis of novel alpha-epoxy-beta-amino acids is described by a route that combines the chemistry of oxazolinyloxiranyllithiums with that of nitrones. The intermediate trioxadiazadispiro[2.0.4.3]undecanes 4 have been isolated and converted by hydrolysis into epoxy-5-isoxazolidinones 5 which can be transformed into the alpha-epoxy-beta-amino acids 8 by N-O reduction.     

New strategy for the stereoselective synthesis of fluorinated beta-amino acids

Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI(2)/NaBH(4) in a nonchelated aprotic medium (dry CH(2)Cl(2)) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.     

Facile and highly stereoselective synthesis of the tetracyclic erythrinane core

A highly stereoselective synthesis of the tetracyclic core of the Erythrina alkaloids is reported through the application of a Meyers bicyclic lactam template.     

p-Nitromandelic acid as a highly acid-stable safety-catch linker for solid-phase synthesis of peptide and depsipeptide acids

[reaction: see text] p-Nitromandelic acid as a safety-catch linker for Boc/Bzl-SPPS of base-labile compounds like peptides and depsipeptides is described. This linker permits acidic removal of side-chain protection groups from the resin. For cleavage from the solid support, the p-nitro group was reduced with tin(II) chloride. After washing off the reducing agents, the (depsi)peptide acids with or without the side-chain protection schemes were obtained by microwave irradiation at 50 degrees C with 5% TFA in dioxane.     

A facile and highly stereoselective synthesis of 1-thiotrehalose

A facile and highly stereoselective synthesis of 1-thiotrehalose, that is, α,α-S-linked trehalose, is described. Glycosylation of configurationally pure α-glucosyl thiol 5 with glucosyl trichloroacetimidate 6 or glucosyl thioimidate 9 followed by deprotection afforded 1-thiotrehalose in excellent α-stereoselectivity and high yield. A different synthetic route to the key building block, α-glucosyl thiol 5, was also investigated in this report.     

A general,highly stereoselective synthesis of amines

The stereochemical course of cycloalkanone imine reductions by a variety of boron hydride reagents is described; very high stereoselectivity with substituted alkali metal borohydrides is reported.     

A stereoselective synthesis of coriolic acid and dimorphecolic acid

Described herein is a convenient synthesis of coriolic acid ($\text{1}$) and dimorphecolic acid ($\text{2}$), the two natural ionophores derived respectively from bovine heart mitochondria and also shown to be self defensive substances in rice plant against rice blast disease.     

An efficient and facile one-step synthesis of highly substituted thiophenes

An efficient one-step method for the synthesis of fully substituted thiophenes, from thiomorpholides and α-halo ketones, was developed. A mechanism has also been proposed for the course of reaction.     

A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin

A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral β-amino acid unit has been achieved through 6 steps from commercially available 2,4,5-trifluorobenzaldehyde 4. The chiral antidiabetic drug was obtained with almost perfect enantiomeric purity (>99.9% ee) in 40.9% overall yield. The key feature of the synthesis is the addition of a malonate enolate to a chiral sulfinylimine in more than 99:1 dr. Our synthetic procedure proved to be highly efficient, economical, and sustainable.     

Creation of a lipase highly selective for trans fatty acids by protein engineering

Sorting out: Protein engineering of lipase CAL-A led to the discovery of mutants with excellent chemoselectivity for the removal of trans and saturated fatty acids from partially hydrogenated vegetable oil. These fatty acids, identified as a major risk factor for human health, can now be removed by enzyme catalysis.     

Nitrile biotransformations for the efficient synthesis of highly enantiopure 1-arylaziridine-2-carboxylic acid derivatives and their stereoselective ring-opening reactions

Catalyzed by the Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions, biotransformations of racemic 1-arylaziridine-2-carbonitriles proceeded efficiently and enantioselectively to produce highly enantiopure S-1-arylaziridine-2-carboxamides and R-1-arylaziridine-2-carboxylic acids in excellent yields. Although the nitrile hydratase exhibits no selectivity against all nitrile substrates, the amidase is highly R-enantioselective towards 1-arylaziridine-2-carboxamides. When treated with benzyl bromide, 1-phenylaziridine-2S-carboxamide underwent a highly regioselective and enantiospecific ring-opening reaction to afford an almost quantitative yield of R-beta-[(benzyl)phenylamino]-alpha-bromopropanamide (C-2 attack) and R-alpha-[(benzyl)phenylamino]-beta-bromopropanamide (C-3 attack) in a 10.5:1 ratio. Further treatment of the resulting ring-opening products with an N-nucleophilic reagent such as amine and azide led to, through most probably the aziridinium intermediate, the formation of S-alpha-substituted-beta-[(benzyl)phenylamino]propanamides in good chemical yields with high enantiomeric purity.     

A novel four-component tandem protocol for the stereoselective synthesis of highly functionalised thiazoles

The reaction of bis(aroylmethyl) sulfides with aromatic aldehydes and ammonium acetate in 1:2:1 molar ratio under solvent-free microwave irradiation afforded predominantly a series of thiazoles, viz., 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-diaryl-2,5-dihydrothiazol-2-yl]ethanones stereoselectively. This reaction presumably occurs via a Knoevenagel condensation-Michael addition-cyclocondensation-ring opening-ring closing Michael addition sequence. The intermediacy of (Z,Z)-2,2′-thiobis(1,3-diarylprop-2-en-1-ones) in the above transformation is demonstrated by their conversion to the thiazoles upon reaction with ammonium acetate under solvent-free microwave irradiation.