sodium hydroxide; Pseudomonas fluorescens MTCCB0015 cell-free extract in phosphate buffer T=37°C; pH=7.50; 20 h;

1: With (S)-(3-OH-4,4-di-Me-2-oxopyrrolidin-1-yl)CH2COOH on resin; triethylamine in tetrahydrofuran T=0°C; 2: With lithium hydroxide in tetrahydrofuran; water T=20°C; 4 h; Further stages. Title compound not separated from byproducts.;

lipase OF I in water T=37°C; pH=3; 36 h;

lithium hydroxide in tetrahydrofuran; water T=20°C; 1 h;

1: 1.) Mg, I2 / 1.) anhydrous THF, 4 h, 60 deg C, 2.) THF 2: 97 percent / H2O, 10percent HCl / methanol / 1 h / Ambient temperature 3: 1.) t-BuOK / 1.) anhydrous THF, 30 min, RT, 2.) THF, RT, 24 h 4: 58 percent / LAH / diethyl ether / 6 h / -78 °C 5: 1.) (L)-(+)-diisopropyl tartrate, 4A sieves, Ti(OiPr)4, t-BuOOH / 1.) CH2Cl2, 1 h, 2.) CH2Cl2, -20 deg C, 3.5 h 6: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 7: LiBr, NCS / methanol / Ambient temperature 8: TsOH / Ambient temperature 9: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 10: H2O, 5percent HCl / methanol / RT, then -20 deg C 11: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme

1: 1.) t-BuOK / 1.) anhydrous THF, 30 min, RT, 2.) THF, RT, 24 h 2: 58 percent / LAH / diethyl ether / 6 h / -78 °C 3: 1.) (L)-(+)-diisopropyl tartrate, 4A sieves, Ti(OiPr)4, t-BuOOH / 1.) CH2Cl2, 1 h, 2.) CH2Cl2, -20 deg C, 3.5 h 4: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 5: LiBr, NCS / methanol / Ambient temperature 6: TsOH / Ambient temperature 7: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 8: H2O, 5percent HCl / methanol / RT, then -20 deg C 9: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme

1: 98 percent / TsOH / benzene / 20 h / Heating 2: 1.) Mg, I2 / 1.) anhydrous THF, 4 h, 60 deg C, 2.) THF 3: 97 percent / H2O, 10percent HCl / methanol / 1 h / Ambient temperature 4: 1.) t-BuOK / 1.) anhydrous THF, 30 min, RT, 2.) THF, RT, 24 h 5: 58 percent / LAH / diethyl ether / 6 h / -78 °C 6: 1.) (L)-(+)-diisopropyl tartrate, 4A sieves, Ti(OiPr)4, t-BuOOH / 1.) CH2Cl2, 1 h, 2.) CH2Cl2, -20 deg C, 3.5 h 7: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 8: LiBr, NCS / methanol / Ambient temperature 9: TsOH / Ambient temperature 10: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 11: H2O, 5percent HCl / methanol / RT, then -20 deg C 12: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme

1: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 2: LiBr, NCS / methanol / Ambient temperature 3: TsOH / Ambient temperature 4: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 5: H2O, 5percent HCl / methanol / RT, then -20 deg C 6: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme

1: 58 percent / LAH / diethyl ether / 6 h / -78 °C 2: 1.) (L)-(+)-diisopropyl tartrate, 4A sieves, Ti(OiPr)4, t-BuOOH / 1.) CH2Cl2, 1 h, 2.) CH2Cl2, -20 deg C, 3.5 h 3: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 4: LiBr, NCS / methanol / Ambient temperature 5: TsOH / Ambient temperature 6: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 7: H2O, 5percent HCl / methanol / RT, then -20 deg C 8: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme

1: 1.) (L)-(+)-diisopropyl tartrate, 4A sieves, Ti(OiPr)4, t-BuOOH / 1.) CH2Cl2, 1 h, 2.) CH2Cl2, -20 deg C, 3.5 h 2: H2, 1M NaOH / 10percent Pd/C / ethanol / Ambient temperature 3: LiBr, NCS / methanol / Ambient temperature 4: TsOH / Ambient temperature 5: 1.) t-BuLi / 1.) Et2O, hexane, -78 deg C, 2.) Et2O, hexane, RT 6: H2O, 5percent HCl / methanol / RT, then -20 deg C 7: RuCl3*H2O, NaIO4 / CCl4; acetonitrile; H2O / Ambient temperature View Scheme