PDF herunterladen
Synlett 2002(12): 2101-2103
DOI: 10.1055/s-2002-35597
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of N-Benzyloxycarbonyl- and N-tert-Butoxycarbonyl-(S)-Isoserine and their Derivatives

Ryszard Andruszkiewicz*, Monika Wyszogrodzka
Department of Pharmaceutical Technology and Biochemistry, GdaÒsk University of Technology, 80-952 GdaÒ sk, Poland
Fax: +48(58)3471144; e-Mail: ryszarda@chem.pg.gda.pl;
Weitere Informationen

Publikationsverlauf

Received 23 September 2002
Publikationsdatum:
20. November 2002 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

A mild and efficient synthesis of N-protected (S)-iso­serine from (S)-malic acid monoester via an oxazolidin-2-one is described.

Key words

amino acids - asymmetric synthesis - oxazolidin-2-ones - ring opening - protecting groups

    References

  • 1a Hettinger TP. Craig LC. Biochemistry  1970,  9:  1224 
    Google Scholar
  • 1b Heaney-Kieras J. Kurylo-Borowska Z. J. Antibiot.  1980,  33:  359 
    Google Scholar
  • 2a Sowinski JF. Toogood PL. Tetrahedron Lett.  1995,  68:  67 
    Google Scholar
  • 2b Kobayashi J. Itagaki F. Shigemori I. Takao T. Shimonishi Y. Tetrahedron  1995,  51:  2525 
    Google Scholar
  • 2c Sowinski JF. Toogood PL. Chem. Commun.  1999,  981 
    Google Scholar
  • 2d Uemoto H. Yahiro Y. Shigemori H. Tsuda M. Takao T. Shimonishi Y. Kobayashi J. Tetrahedron  1998,  54:  6719 
    Google Scholar
  • 2e Dohren H. von Kleinkauf H. Biotechnology  1999-2001,  7:  313 
    Google Scholar
  • 3a Schmidt EW. Bewley CA. Faulkner DJ. J. Org. Chem.  1998,  63:  1254 
    CrossrefGoogle Scholar
  • 3b Moore BS. Nat. Prod. Rep.  1999,  16:  653 
    CrossrefGoogle Scholar
  • 4a Matsunaga S. Fusetani N. J. Org. Chem.  1995,  60:  1177 
    CrossrefGoogle Scholar
  • 4b Taylor CM. Tetrahedron  1998,  54:  11317 
    CrossrefGoogle Scholar
  • 5 Bewley C. Faulkner DJ. J. Org. Chem.  1994,  59:  4849 
    Google Scholar
  • 6a Wright JJ. Cooper A. Daniels PJL. Nagabhushan TL. Rane D. Turner WN. Weinstein J. J. Antibiot.  1976,  29:  714 
    CrossrefGoogle Scholar
  • 6b Haskell TH. Rodebaugh R. Plessas N. Watson D. Westland RD. Carbohydr. Res.  1973,  28:  263 
    CrossrefGoogle Scholar
  • 7 Floreancig PE. Swalley SE. Trauger JW. Dervan PB. J. Am. Chem. Soc.  2000,  122:  6342 
    CrossrefGoogle Scholar
  • 8 For a review see: Andruszkiewicz R. Pol. J. Chem.  1998,  72:  1 
    Google Scholar
  • 9a Andruszkiewicz R. Walkowiak A. Org. Prep. Proc. Int.  2001,  33:  379 
    Google Scholar
  • 9b

    Czajgucki, Z.; Sowinski, P.; Andruszkiewicz, R. Amino Acids 2002, in press.
  • 10a Andruszkiewicz R. Milewski S. Borowski E. J. Enzyme Inhib.  1995,  9:  123 
    Google Scholar
  • 10b Andruszkiewicz R. Jedrzejczak R. Zieniawa T. Wojciechowski M. Borowski E. J. Enzyme Inhib.  2000,  15:  429 
    Google Scholar
  • 11 Cammas S. Renard I. Boutault K. Guerin P. Tetrahedron: Asymmetry  1993,  4:  1925 
    CrossrefGoogle Scholar
  • 15a

    Representative Experimental Procedure: Compound 5a-5c (5 mmol) was quickly dissolved in dry THF (50 mL) and cooled under argon to -40 °C. Benzyltrimethyl-ammonium hydroxide (5.5 mL of 40% solution in methanol, 10.5 mmol) was added over 20 min to the solution of 5a-5c and stirred for an additional 1 h. HOAc (1.1 mL) and water (2.5 mL) were then added and the reaction mixture was warmed to r.t. and the solvent was evaporated under reduced pressure. The residue was extracted with EtOAc (2 × 50 mL). The extracts were washed, dried over MgSO4 and evaporated. The solid residue was crystallized from a mixture of EtOAc and hexane to yield 6a (0.77 g, 75%). Mp: 93-94 °C; [α]D +6.4 (c 2.5, MeOH). Similarily, 6b was also obtained (0.89 g, 75%). Mp: 117-119 °C; [α]D +3.2 (c 2.5, MeOH). Physical and spectral data for 6a and 6b are in agreement with literature values, see ref. [15b]

    Crossref
  • 15b Burger K. Windeisen E. Pires R. J. Org. Chem.  1995,  60:  7641 
    CrossrefGoogle Scholar
12

Typical Procedure for the Preparation of 4a and 4b: The appropriate substrate 2a,b (5 mmol), and DPPA (1.18 mL, 5.5 mmol) were dissolved in t-BuOH (20 mL). The reaction flask was flushed with argon, and Et3N (0.75 mL, 5.5 mmol) was added. The reaction mixture was refluxed for 4 h and cooled to r.t. The solvent was removed under reduced pressure, the residue dissolved in EtOAc (50 mL). In the case of 4a, the solution was washed with sat. NaHCO3 solution, water and finally dried over anhyd MgSO4. After evaporation of the solvent, the solid residue was crystallized from EtOAc and hexane to yield 4a (0.77 g, 70%). Mp: 128-129 °C; [α]D +10.0 (c 1, EtOAc). 1H NMR (200 MHz, CDCl3): δ = 3.66-3,74 (dd, J 4a,4b = 9.5 Hz, J 4a,5a = 5.6 Hz, 1 H CHCH 2 , 4Ha), 3.85-3.95 (dd, J 4b,4a = 9.5 Hz, 1 H, CHCH 2 , 4 Hb), 5.05-5.10 (dd, J 5a,4b = 9.5 Hz, J 5a,4a = 5.6 Hz, 1 H, CHCH2, 5 Ha), 5.28 (s, 2 H, CH 2 C6H5), 5.9 (br s, 1 H, NH), 7.40(s, 5 H, C 6 H 5 ). Anal. Calcd for C11H11NO4: C, 59.73; H, 5.01; N, 6.33. Found: C, 59.58; H, 5.12; N, 6.38. In the case of 4b, after evaporation of the solvent, the product was purified by column chromatography (silica gel, hexane-ethyl acetate 2:3) furnishing 4b (0.58g, 80%) which was crystallized from ethyl acetate and hexane. Mp: 95-97 °C; [α]D +20.1 (c 1, EtOAc). 1H NMR (200 MHz, CDCl3): δ = 3.65-3.75(dd, J 4a,4b = 9.6 Hz, J 4a,5a = 5.5 Hz, 1 H, CHCH 2 , 4 Ha), 3.85 (s, 3 H, CH 3 ), 3.86-3.96 (dd, J 4a,4b = 9.6, J 4b,5a = 5.5 Hz, 1 H, CHCH 2 , 4 Hb), 5.01-5.09 (dd, J 5a,4b = 9.6 Hz, J 5a,4b = 5.5 Hz, 1 H, CHCH2, 5 Ha), 6.24
(br s, 1 H, NH). Anal. Calcd for C5H7NO4: C, 41.38; H, 4.86; N, 9.65. Found: C, 41.22; H, 4.74; N, 9.60.

13

Typical Procedure, 4a,b to 5a-5c: Compound 4a or 4b (9 mmol), DMAP (25 mg) and Et3N (1.5 mL, 11 mmol) were dissolved in dry THF (25 mL) and cooled in an ice bath. A solution of (Boc)2O (2.05 g, 9.4 mmol) in THF (8 mL) was added to a stirred reaction mixture over 20 min. The temperature of the reaction was kept between 5 °C and 10 °C overnight. Then, equimolar amounts of NaHSO4 (1.32 g, 11 mmol) in water (10 mL) were added. After evaporation of the solvent under reduced pressure, the white suspension was dissolved in EtOAc (50 mL), and the solution was washed with dilute NaHSO4 solution, water and finally dried (MgSO4) and evaporated. The solid was crystallized from diethyl ethyl ether and hexane to give 5a (2.5 g, 85%). Mp: 130-131 °C; [α]D +24.0 (c 1, EtOAc). 1H NMR (200 MHz, CDCl3): δ = 1.56 [s, 9 H (CH 3 )C],. 4.00-4.07 (dd, J 4a,4b = 10.7, J 4a,5a = 5.5 Hz, 1 H, CHCH 2 , 4 Ha), 4.14-4.24 (dd, J 5a,4b = 9.5 Hz, J 4a,4b = 10.7 Hz, 1 H, CHCH 2 , 4 Hb), 4.91-4.99 (dd, J 5a,4b = 9.5 Hz, J 5a,4a = 5.5 Hz, 1 H, CHCH2), 5.29 (s, 2 H, CH 2 C6H5), 7.40 (s, 5 H, C 6 H 5 ). Anal. Calcd for C16H19NO6: C, 59.18; H, 5.96; N, 4.36. Found: C, 59.34; H, 5.92; N, 4.22. In the same manner compound 5c was obtained (1.54 g, 70%). Mp: 76-78 °C; [α]D +36.8 (c 2.5, MeOH). 1H NMR (200 MHz, CDCl3): δ = 1.55 [s, 9 H (CH 3 )C], 3.87 (s, 3 H, CH3), 4.00-4.08 (dd, J 4a,4b = 10.7, J 4a,5a = 5.5 Hz, 1 H, CHCH 2 , 4Ha), 4.14-4.25 (dd, J 5a,4b = 9.5 Hz, J 4a,4b = 10.7 Hz, 1 H, CHCH 2 , 4 Hb), 4.89-4.97 (dd, J 5a,4b = 9.5 Hz, J 5a,4a = 5.5 Hz, 1 H, CHCH2). Anal. Calcd for C10H15NO6: C, 48.98; H, 6.17; N, 5.71. Found: C, 49.17; H, 6.22; N, 5.58.

14

Synthesis of 5b: (5S)-5-Benzyloxycarbonyl-2-oxazol-idinone 4a (1.99 g, 9 mmol) was dissolved in THF (30 mL) and Et3N (10 mL). The reaction mixture was cooled to
-20 °C. A solution of benzyl chloroformate (2.6 mL, 18 mmol) in THF (3.3 mL) was slowly added over 20 min. The stirred reaction mixture was then kept at -10 °C overnight. The reaction mixture was quickly neutralized with a stoichiometric amount of cold 10% aq solution of NaHSO4 and extracted with EtOAc (2 × 50 mL). The extracts were washed with water, dried (MgSO4) and evaporated. The solid residue was dissolved in a small volume of hot EtOAc and diluted with a large volume of diethyl ether. Crystals were collected to give 5b (2.4g, 80%). Mp: 112-114 °C; [α]D +24.0 (c 2.5, EtOAc). 1H NMR (200 MHz, CDCl3):
δ = 4.04-4.12 (dd, J 4a,4b = 10.6, J 4a,5a = 5.5 Hz, 1 H, CHCH 2 , 4Ha), 4.18-4.28 (dd, J 5a,4b = 9.5 Hz, J 4a,4b = 10.6 Hz, 1 H, CHCH 2 , 4 Hb), 4.93-5.01 (dd, J 5a,4b = 9.5 Hz, J 5a,4a = 5.5 Hz, 1 H, CHCH2), 5.27 (s, 2 H, CH 2 C6H5-benzyl ester), 5.31 (s, 2 H, CH 2 C6H5-benzyloxycarbonyl group), 7.35-7.45 (br s, 10 H, 2 × C 6 H 5 ). Anal. Calcd for C19H17NO6: C, 64.22; H, 4.82; N, 3.94. Found: C, 64.34; H, 4.68; N, 3.88.

16

Preparation of 7a: Compound 5a (0.64 g, 2 mmol) was dissolved in a mixture of THF (10 mL) and MeOH (15 mL) and palladium on activated carbon (5%, 50 mg) was added. The reaction flask was flushed with hydrogen and the hydrogenation was performed at atmospheric pressure for 1 h at r.t. The catalyst was filtered off and the solvents were evaporated. The residue was crystallized from a mixture of EtOAc and hexane to give 7a (0.43g, 94%). Mp: 99-100 °C; [α]D +28.2 (c 1, MeOH). 1H NMR (500 MHz, CDCl3): δ = 1.56 [s, 9 H (CH 3 )C],. 4.08-4.11 (dd, J 4a,4b = 10.7, J 4a,5a = 5.4 Hz, 1 H, CHCH 2 , 4 Ha), 4.21-4.25 (dd, J 5a,4b = 9.8 Hz, J 4a,4b = 10.7 Hz, 1 H, CHCH 2 , 4 Hb), 4.95-4.98 (dd, J 5a,4b = 9.8 Hz, J 5a,4a = 5.4 Hz, 1 H, CHCH2). Anal. Calcd for C9H13NO6: C, 46.75; H, 5.67; N, 6.06. Found: C, 46.78; H, 5.52; N, 5.98.