(3'aS,4R,7'aS)-2,2,2',2'-tetramethylspiro[1,3-dioxolane-4,6'-4,7a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyran]-7'-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,4-Anhydro-D-glucitol may be prepared using the procedure disclosed in Acta Chem. Scand., B35, 441-449 (1981), whereby D-sorbitol is heated with an aqueous mineral acid such as sulfuric acid. The L-enantiomer, 1,4-anhydro-L-glucitol, may be prepared from L-glucitol by an analogous procedure. L-glucitol may be prepared by sodium borohydride reduction of L-glucose. The D and L enantiomers may simply be combined to form a 1,4-anhydro-DL-glucitol mixture.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Chemical synthesis of 4-ketoproline derivatives from inexpensive achiral starting materials will typically produce a racemic mixture of two enantiomers. It has been reported that hydrogenation of either D- or L-enantiomer of 4-ketoproline derivatives can produce the corresponding cis-4-hydroxyproline derivatives with high selectivity (Kuhn et al., Chem. Ber. 89:1423 (1956)), so an enzymatic resolution of a racemic mixture of D- and L-4-ketoproline derivatives would allow for the hydrogenation of the 4-keto-D-proline derivative to produce CHDP. Chemical or enzymatic racemization of the remaining 4-keto-L-proline derivative to a 50/50 mixture of D- and L-isomers could allow the undesired L-isomer to be recycled back into the resolution step. Alternatively, if the 4-keto-L-proline derivative could be reduced and hydrolyzed to THLP, the THLP is readily converted to CHDP by chemical isomerization. will typically produce a racemic mixture of two enantiomers

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Chemical synthesis of 4-ketoproline derivatives from inexpensive achiral starting materials will typically produce a racemic mixture of two enantiomers. It has been reported that hydrogenation of either D- or L-enantiomer of 4-ketoproline derivatives can produce the corresponding cis-4-hydroxyproline derivatives with high selectivity (Kuhn et al., Chem. Ber. 89:1423 (1956)), so an enzymatic resolution of a racemic mixture of D- and L-4-ketoproline derivatives would allow for the hydrogenation of the 4-keto-D-proline derivative to produce CHDP. Chemical or enzymatic racemization of the remaining 4-keto-L-proline derivative to a 50/50 mixture of D- and L-isomers could allow the undesired L-isomer to be recycled back into the resolution step. Alternatively, if the 4-keto-L-proline derivative could be reduced and hydrolyzed to THLP, the THLP is readily converted to CHDP by chemical isomerization. will typically produce a racemic mixture of two enantiomers

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXXVIII) (35 g, 100 mmol) in Et2O (600 mL) was added quinine (34 g, 100 mmol) in portions. The reaction was stirred at room temperature for 30 min at which time the white precipitate (L-enantiomer salt) was filtered and washed with Et2O. The solid was taken up in EtOAc/aqueous KHSO4. The organic layer was washed with aqueous KHSO4, brine and dried over MgSO4. The solvent was removed in vacuo to give optically pure (Marfey test) (2S,3R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXXIX) (12 g, 34 mmol, 68% yield). 1H NMR (DMSO-d6) δ ppm 1.33 (s, 9H), 4.09 (brs, 1H), 5.13 (brs, 1H), 5.56 (brs, 1H), 7.47 (d, J=8 Hz, 2H), 7.56 (d, J=8 Hz, 2H); 19F NMR (DMSO-d6) δ ppm −60.15; ESIMS found for C15H18F3NO5 m/z 348 (M−H) was filtered washed with Et2O The organic layer was washed with aqueous KHSO4, brine dried over MgSO4 The solvent was removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,4-Anhydro-D-glucitol may be prepared using the procedure disclosed in Acta Chem. Scand., B35, 441-449 (1981), whereby D-sorbitol is heated with an aqueous mineral acid such as sulfuric acid. The L-enantiomer, 1,4-anhydro-L-glucitol, may be prepared from L-glucitol by an analogous procedure. L-glucitol may be prepared by sodium borohydride reduction of L-glucose. The D and L enantiomers may simply be combined to form a 1,4-anhydro-DL-glucitol mixture.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: L-sorbose is an important intermediate for the synthesis of L-ascorbic acid (vitamin C) by the Reichstein method (see FIG. 1). When D-sorbitol is chemically oxidized, approximately a half of the product becomes D-sorbose, whereas when D-sorbitol is brought into contact with a microorganism having an SLDH activity, only an L-enantiomer is obtained in a yield of about 95%. Therefore, a fermentation method has been conventionally used for converting D-sorbitol to L-sorbose.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: L-sorbose is an important intermediate for the synthesis of L-ascorbic acid (vitamin C) by the Reichstein method (see FIG. 1). When D-sorbitol is chemically oxidized, approximately a half of the product becomes D-sorbose, whereas when D-sorbitol is brought into contact with a microorganism having an SLDH activity, only an L-enantiomer is obtained in a yield of about 95%. Therefore, a fermentation method has been conventionally used for converting D-sorbitol to L-sorbose.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cysteine is an amino acid with one chiral carbon atom. It exists as an L-enantiomer, a D-enantiomer or a racemic mixture of the L- and D-enantiomers. The L-enantiomer is the naturally occurring configuration. a D-enantiomer or a racemic mixture of the L- and D-enantiomers

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (±)-2-Amino-5-phenylpentanoic acid (35 g) was suspended in water (3 L) and solubilized by adjusting the pH to 12 with 7N sodium hydroxide solution. The pH was readjusted to pH 8 using 1M phosphoric acid with continuous stirring at 45° C. The solution was allowed to cool to 40° C. and L-amino acid oxidase (Sigma, 0.7 unit/mg) was added. The reaction was stirred with good aeration at 37°-40° C. for two weeks. The reaction was monitored using the following High Pressure Liquid Chromatography (HPLC) system: C-18 Waters analytical column, 20% acetonitrile in Buffer (0.624 g/L CuSO4.5H2O, 0.576 g/L L-proline, 2 g/L ammonium acetate, and 1L of water with the pH of the solution adjusted to pH 7 with ammonium hydroxide); 2 mL/minute flow rate; fluorescence detection: Ex 345 nm, Em>415 nm; OPA derivatization: 300 μL of 1N sodium borate pH 9.4, 50 mL of 20 mg ortho-phthalaldehyde (OPA) plus 24 ng N-acetyl cysteine/6 mL 50% methanol/water; incubate 3 minutes at ambient temperature. When the digestion of the L-enantiomer was complete, the reaction mixture was concentrated to 500 mL by removing water in vacuo. The pH was adjusted to 5 and the predpitate was collected by filtration and recrystallization from ethanol-water to afford 17.32 g (99%) of the title compound. to cool to 40° C. The reaction was stirred with good aeration at 37°-40° C. for two weeks incubate 3 minutes at ambient temperature the reaction mixture was concentrated to 500 mL by removing water in vacuo the predpitate was collected by filtration and recrystallization from ethanol-water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Chemical synthesis of 4-ketoproline derivatives from inexpensive achiral starting materials will typically produce a racemic mixture of two enantiomers. It has been reported that hydrogenation of either D- or L-enantiomer of 4-ketoproline derivatives can produce the corresponding cis-4-hydroxyproline derivatives with high selectivity (Kuhn et al., Chem. Ber. 89:1423 (1956)), so an enzymatic resolution of a racemic mixture of D- and L-4-ketoproline derivatives would allow for the hydrogenation of the 4-keto-D-proline derivative to produce CHDP. Chemical or enzymatic racemization of the remaining 4-keto-L-proline derivative to a 50/50 mixture of D- and L-isomers could allow the undesired L-isomer to be recycled back into the resolution step. Alternatively, if the 4-keto-L-proline derivative could be reduced and hydrolyzed to THLP, the THLP is readily converted to CHDP by chemical isomerization. will typically produce a racemic mixture of two enantiomers