• Archives of Pharmacal Research
• /
• 제29권1호
• /
• pp.108-111
• /
• 2006

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt with R-(+)-$\alpha$-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and $^1H-NMR$ method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.

• KSBB Journal
• /
• 제9권3호
• /
• pp.306-311
• /
• 1994

유기용매상에서 Bacillus licheniformis에서 생산되는 protease를 이용하여 라세믹 ${\alpha}$-methylbenzy lamine의 광학분함을 행하였다. 이 반응은 아설 제 공자로 활성 에스대르를 샤용하여 라서l믹 아민을 광 학선택적으로 아마드로 변환시킨다. 이 반응의 반응 속도와 광학선택성을 증가시켜주기 위해 효소를 완 충액에 녹여 pH를 맞춘 후에 동결건조시키거나, 동결건조시 염이나 lyoprotectants를 첨가시키는 방 법, 적당한 유기용매의 선정, 에스테르 구조의 디자 인 등의 방법을 사용하였다. 그 결과. 30배의 초기 반응속도의 증가 및 12배의 광학선택성이 증가하는 결과를 보였다.

• 약학회지
• /
• 제39권4호
• /
• pp.433-437
• /
• 1995

Optically pure(-)-and (+)-$\alpha$-hydroxy-$\alpha$-(p-chlorobiphenyl)acetic acids were prepared. The racemate was synthesized through three steps. By condensation of p-cnorobiphenyl with diethyl ketomalonate in the presence of SnCl$_{4}$, diethyl $\alpha$-hydroxy-$\alpha$-(p-chlorobiphenyl)malonate (1) was formed and subsequently ($\pm$)-$\alpha$-hydroxy-$\alpha$-(p-chlorobiphenyl)acetic acid (3) was obtained through hydrolysis and decarboxylation. For the separation of the racemate the classical resolution method, derivatization of a racemate by reaction with an optically pure compound was employed. In this case the optically pure compound were [R]-(+)-$\alpha$-methylbenzylamine and [S]-(-)-$\alpha$-methylbenzylamine. Diastereomeric salts between acids and bases could be easily separated by crystallization in absolute ethanol.

• Journal of Applied Biological Chemistry
• /
• 제43권2호
• /
• pp.101-103
• /
• 2000

The synthesis and resolution of ($\pm$)-10,11-dihydroxydibenzosuberenone 3, a potential pharmaceutical compound, is described. It was synthesized from the 5H-dibenzo[a,d]cycloheptene-5-one (dibenzosuberenone) 1, and converted to diastereomeric isomers using (R)-(+)-$\alpha$-methylbenzylamine. Optical resolution of ($\pm$)-10,11-dihydroxydibenzosuberenone 3 was possible by fractional recrystallization of the diastereomer formed in ethanol. The optical resolution of 10,11-dihydroxydibenzosuberenone through formation of its phosphoamidates 5 using the (R)-(+)-$\alpha$-methylbenzylamine was achieved. These compounds provided the optical rotation of [${\alpha}]=-64.3$ for (-)-10,11-dihydroxy-dibenzosuberenone and [${\alpha}]=+61.3$ for (+)-10,11-dihydroxydibenzosuberenone. The (-)- and (+)-enantiomers were prepared in five steps from dibenzosuberenone with overall yields of 11.66% and 9.38%, respectively.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.223.3-224
• /
• 2003

Chiral discrimination of ibuprofen by $^1$H-NMR using several chiral solvating agents such as (-)-brucine, (-)-cinchonidine, (1R, 2S)-(-)-ephedrine, (S)-(-)-${\alpha}$- methylbenzylamine, (-)-strychnine and L-(-)-tryptophane was investigated. Racemic ibuprofen treated with one equivalent of chiral solvating agent was preferentially crystallized. Chiral purity of each precipitates was measured by chiral HPLC and chemical shift differences(ΔΔ$\delta$) was calculated. Eventhough (S)-(-)-${\alpha}$-methylbenzylamine was most effective for the preferential recrystalization of (S)-(+)-ibuprofen, chemical shift differentiation ability was weak. (omitted)

• 약학회지
• /
• 제41권1호
• /
• pp.18-21
• /
• 1997

Synthesis of an optically active azabicyclo[3.2.1]octane skeleton as a backbone of the tropane alkaloids has been achieved by employing intramolecular Mannich reaction. Utilizat ion of (R)-${\alpha}$-methylbenzylamine as a chiral auxiliary provided an excellent cyclization of amino dioxolane precursor. However, this auxiliary did not afford high asymmertic induction for the preparation of the optically active cyclization precursor.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.219.1-219.1
• /
• 2003

$^1$H-NMR method for the determination of enantiomeric purity of (S)-(+)-ibuprofen was developed using (-)-cinchonidine as a chiral solvating agent. (S)-(+)-ibuprofen was prepared by optical resolution of racemic ibuprofen using preferential recrystallization method with (S)-(-)-${\alpha}$-methylbenzylamine and (R)-(-)-ibuprofen by semi-preparative chiral HPLC using chiral OD column and n-hexane/2-propanol/trifluoroacetic acid as a mobile phase. Several concentrations of synthetic mixture of (S)-(+)-ibuprofen and (R)-(-)-ibuprofen were added to the (-)-cinchonidine disolved in CDCl$_3$. (omitted)