28624-52-4

Upstream product

• 110919-15-8 (4R,6R)-2-((R)-2,2-Dimethyl-cyclopropyl)-4,6-dimethyl-[1,3]dioxane 
• 1740-74-5 1,1-diethoxy-3-methyl-2-butene 
• 167482-50-0 1,2-O-Isopropylidene-3-O-(p-phenylbenzyl)-4,5-O-<(1'R)-3'-methyl-2'-buten-1'-yl>-β-D-fructopyranose 
• 1759-55-3 (RS)-2,2-dimethylcyclopropanecarboxamide 
• 110919-09-0 (4R,6R)-4,6-Dimethyl-2-(2-methyl-propenyl)-[1,3]dioxane 
• 107-86-8 3,3-dimethyl acrylaldehyde 

Downstream Products

• 50675-57-5 dl-2,2-dimethylcyclopropane-1-carboxylic acid chloride 

Relevant academic research and scientific papers

Industrial production of S-2,2-dimethylcyclopropanecarboxamide with a novel recombinant R-amidase from Delftia tsuruhatensis

R-Stereoselective amidase, a key enzyme responsible for the formation of chiral center of cilastatin, has been cloned from Delftia tsuruhatensis and expressed in Escherichia coli under T7 promoter. This recombinant amidase exhibits strict R-selectivity towards 2,2-dimethylcyclopropanecarboxamide (DMCPCA). The amidase activity of the engineered E. coli strain reached 2963 U/L in a 5-L bioreactor, which was 8.27 times higher than that of D. tsuruhatensis, and was further increased to 5255 U/L in a 100-L bioreactor. Using cell-free extract prepared from 1 kg (wet cell weight) of recombinant E. coli cells as catalyst, 60 kg of R,S-DMCPCA was resolved into S-DMCPCA (28.6 kg) and R-2,2-dimethylcyclopropanecarboxylic acid (R-DMCPCS 31.7 kg) in 18 h, and the enantiomeric excess (ee) value of S-DMCPCA reached 99.32%. During the purification process, 24.6 kg of S-DMCPCA was eluted from adsorption resin HZ801 with 80% (v/v) acetone, and then 20.5 kg of pure S-DMCPCA was obtained after concentration and crystallization, corresponding to a total yield of 34.2% from R,S-DMCPCA. Therefore, the industrial production process of S-DMCPCA was successfully established using recombinant R-amidase from D. tsuruhatensis.

Kinetic resolution of (R,S)-2,2-dimethylcyclopropanecarboxamide by Delftia tsuruhatensis ZJB-05174: Role of organic cosolvent in reaction medium

Both enantioselectivity and catalytic activity were greatly enhanced in Delftia tsuruhatensis ZJB-05174 catalyzed kinetic resolution of 2,2-dimethlycyclopropanecarboxamide in the presence of ethanol and acetonitrile. The enantiomeric ratio (E) rose from 27 to 140 and 90 by addition of 5% acetonitrile and ethanol, respectively. In the scaled-up biotransformation, the reaction time was shortened to 1.33 h with an ees of 99% and 12.4 g of optically pure product (43.5% total yield) was afforded. These results indicated that addition of cosolvent was a simple and practical tool to improve amidase properties and would be extensively applied in amidase-catalyzed bioprocess.

Production of L-tryptophan by enantioselective hydrolysis of d,l-tryptophanamide using a newly isolated bacterium

Bacterial strain ZJB-09211 capable of amidase production has recently been isolated from soil samples. The strain is able to asymmetrically hydrolyze l-tryptophanamide from d,l-tryptophanamide to produce l-tryptophan in high yield and with excellent stereoselectivity (enantiomeric excess > 99.9 %, and enantiomeric ratio > 200). Strain ZJB-09211 has been identified as Flavobacterium aquatile based on the cell morphology analysis, physiological tests, and the 16S rDNA sequence analysis. Optimization of the fermentation medium led to an about six-fold increase in the amidase activity of strain ZJB-09211, which reached 501.5 U L-1. Substrate specifity and stereoselectivity investigations revealed that amidase of F. aquatile possessed a broad substrate spectrum and high enantioselectivity.

Highly Enantioselective Intermolecular Cyclopropanation Catalyzed by Dirhodium(II) Tetrakis[3(S)-phthalimido-2-piperidinonate]: Solvent Dependency of the Enantioselection

The enantioselectivity in cyclopropanations catalyzed by dirhodium(II) tetrakis[3(S)-phthalimido-2-piperidinonate] has been found to be substantially improved by employing ether as the rarely used solvent. Cyclopropanations of styrenes or 1,1-disubstituted alkenes with 2,4-dimethyl-3-pentyl diazoacetate in ether are promoted by this catalyst to afford the corresponding cyclopropane products in the highest levels of enantioselectivity (up to 98% ee) reported to date for the dirhodium(II)-catalyzed intermolecular cyclopropanation reactions.

Asymmetric Cyclopropanation Using New Chiral Auxiliaries Derived from D-Fructose

Acetals of α,β-unsaturated aldehydes with 3-O-alkylated derivatives of 1,2-O-isopropylidene-β-D-fructopyranose and 1,2-O-isopropylidene-β-D-psicopyranose, which are readily available from D-fructose, were cyclopropanated with Et2Zn and CH2I2 with good diastereoselectivity.The effects of structure of the acetals on enantioselectivity were examined.

ASYMMETRIC SIMMONS-SMITH REACTIONS USING HOMOCHIRAL PROTECTING GROUPS

Asymmetric Simmons-Smith reactions of α,β-unsaturated acetals derived from chiral dialkyl tartrate or (2R,4R)-2,4-pentanediol are described.Treatment of the acetal with diethylzinc and methylene iodide gives a cyclopropane with high diastereoselectivity.The acetal group is readily transformed to the aldehyde or the ester group.In addition, the method is successfully applied to the enantioselective synthesis of 5,6-methanoleukotriene A4, a stable and selective inhibitor of leukotriene biosynthesis.