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Synlett 2003(15): 2374-2376  
DOI: 10.1055/s-2003-42115
LETTER
© Georg Thieme Verlag Stuttgart · New York

Lipase-Catalyzed Kinetic Resolution of 4-(N-Boc-amino)-1-alken-3-ols

Tetsuta Oshitari, Tadakatsu Mandai*
Department of Chemistry and Bioscience, Kurashiki University of Science and the Arts, 2640 Nishinoura, Tsurajima, Kurashiki 712-8505, Japan
Fax: +81(86)4401062; e-Mail: ted@chem.kusa.ac.jp;
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Publication History

Received 19 September 2003
Publication Date:
23 October 2003 (online)

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Abstract

A wide range of 4-(N-Boc-amino)-1-alken-3-ols were efficiently resolved by lipase-catalyzed kinetic resolution. This procedure has been successfully applied to the highly enantioselective synthesis of the taxol side chain.

Key words

4-(N-Boc-amino)-1-alken-3-ols - kinetic resolution - lipase - the taxol side chain

    References

  • 1 Gargano JM. Lees WJ. Tetrahedron Lett.  2001,  42:  5845 ; and references therein
    CrossrefGoogle Scholar
  • 2a Umezawa H. Aoyagi T. Morishima H. Matsuzaki M. Hamada M. Takeuchi T. J. Antibiot.  1970,  23:  259 
    CrossrefGoogle Scholar
  • 2b Yoo D. Oh JS. Kim YG. Org. Lett.  2002,  4:  1213 ; and references therein
    CrossrefGoogle Scholar
  • 3 Jost S. Gimbert Y. Green AE. Fotiadu F. J. Org. Chem.  1997,  62:  6672 ; and references therein
    CrossrefGoogle Scholar
  • 4a Sobin BA. Tanner FW. J. Am. Chem. Soc.  1954,  76:  4053 
    CrossrefGoogle Scholar
  • 4b Hulme AN. Rosser EM. Org. Lett.  2002,  4:  265 ; and references therein
    CrossrefGoogle Scholar
  • 5a Kulanthaivel P. Hallock YF. Boros C. Hamilton SM. Janzen WP. Ballas LM. Loomis CR. Jiang JB. Katz B. Steiner JR. Clardy J. J. Am. Chem. Soc.  1993,  115:  6452 
    Google Scholar
  • 5b Fürstner A. Thiel OR. J. Org. Chem.  2000,  65:  1738 ; and references therein
    Google Scholar
  • 6a Kobayashi S. Ueno M. Suzuki R. Ishitani H. Tetrahedron Lett.  1999,  40:  2175 
    Google Scholar
  • 6b Kikuchi H. Tasaka H. Hirai S. Takaya Y. Iwabuchi Y. Ooi H. Hatakeyama S. Kim H.-S. Wataya Y. Oshima Y. J. Med. Chem.  2002,  45:  256 3; and references therein
    Google Scholar
  • 7 Ager DJ. Prakash I. Schaad DR. Chem. Rev.  1996,  96:  835 
    CrossrefPubMedGoogle Scholar
  • 8a Review: Johnson RA. Sharpless KB. In Catalytic Asymmetric Synthesis   Ojima I. VCH; New York: 1993.  p.103 
    CrossrefGoogle Scholar
  • 8b Sharpless KB. Amberg W. Bennani YL. Crispino GA. Hartung J. Jeong K.-S. Kwong H.-L. Morikawa K. Wang Z.-M. Xu D. Zhang X.-L. J. Org. Chem.  1992,  57:  2768 
    CrossrefGoogle Scholar
  • 8c Bruncko M. Schlingloff G. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1997,  36:  1483 
    CrossrefGoogle Scholar
  • 9 Mandai T. Oshitari T. Susowake M. Synlett  2002,  1665 
    Article in Thieme ConnectGoogle Scholar
  • 13a Chen C.-S. Fujimoto Y. Girdaukas G. Sih CJ. J. Am. Chem. Soc.  1982,  104:  7294 
    CrossrefGoogle Scholar
  • 13b Chen C.-S. Wu S.-H. Girdaukas G. Sih CJ. J. Am. Chem. Soc.  1987,  109:  2812 
    CrossrefGoogle Scholar
  • 14a (3R,4R)-3-OAc was methanolyzed (K2CO3/MeOH, r.t., 40 min) to the corresponding alcohol (3R, 4R)-3, which was analyzed by HPLC (Chiralcel OD-H, hexane-2-propanol = 4:1, 254 nm). (3R,4S)-4-OAc and (3S,4R)-4 were converted to the corresponding phenyl carbamates (PhNCO/Py, r.t., 6 h), which were analyzed by HPLC (Chiralcel OD-H, hexane-2-propanol = 5:1, 254 nm). Ohno reported that the modification of a protecting group at amino moiety changes the enantioselectivity of esterase-catalyzed hydrolysis of esters: Ohno M. Kobayashi S. Iimori T. Wang Y.-F. Izawa T. J. Am. Chem. Soc.  1981,  103:  2405 
    CrossrefGoogle Scholar
  • 14b

    In our case, the reverse of the enantioselectivity was not observed.
    Crossref
  • 15a

    Prepared as follows: A mixture of 2-phenyl-3-hydroxy-4-pentenoic acids (anti/syn = 10:1), readily available by the Mulzer’s protocol, [15b] was subjected to Curtius reaction to give a trans cyclic carbamate as the sole product.
    Crossref
  • 15b Mulzer J. Segner J. Brüntrup G. Tetrahedron Lett.  1977,  4651 
    CrossrefGoogle Scholar
  • 15c

    The corresponding cis cyclic carbamate was not produced probably due to the intensive retro-aldol reaction of the intermediary β-hydroxy acyl azide. Syn (±)-5 was provided in good yield after N-protection followed by ring opening (Scheme [5] ).

    Scheme 5 Reagents and conditions: (a) LDA (2.1 equiv), 0 °C, 1 h, concentrated to dryness; (b) acrolein-THF, 0 °C-r.t., 48 h; (c) DPPA-Et3N-toluene; (d) Boc2O-Et3N-DMAP, THF, 54% in 3 steps; (e) Cs2CO3-MeOH, r.t., 12 h, 75%.
    Crossref
  • 17 Wang Z.-M. Kolb HC. Sharpless KB. J. Org. Chem.  1994,  59:  5104 
    Google Scholar
10

Prepared as shown below (Scheme [4] ).

Scheme 4 Reagents and conditions: (a) LDA, -78 °C, acrolein; (b) 1 M NaOH-MeOH, H+; (c) DPPA-Et3N-toluene; (d) Boc2O-Et3N-DMAP-toluene, r.t., 6 h; (e) Separation by medium-pressure column chromatography (SiO2); (f) Cs2CO3-MeOH, r.t., 12 h.

11

The enantiomeric purities of (3R,4R)-1-OAc, (3S,4S)-1, (3R,4S)-2-OAc, and (3S,4R)-2 were analyzed by HPLC (Chiralcel OD-H or Chiralcel OJ-H, hexane-2-propanol) after being converted to suitably protected compounds as described below (Figure [1] ).

Figure 1 1a: R′ = CONHPh, OD-H, 50:1, 230 nm; 1b: R′ = CONHPh, OD-H, 30:1, 230 nm; 1c: R′ = CONHPh, OD-H, 20:1, 254 nm; 1d: R′ = Bz, OD-H, 50:1, 254 nm; 1e: R′ = H, OJ-H, 50:1, 230 nm; 2a: R′ = Bz, OD-H, 50:1, 254 nm; 2b: R′ = Bz, OD-H, 50:1, 254 nm; 2c: R′ = H, OD-H, 20:1, 230 nm; 2d: R′ = H, OD-H, 20:1, 230 nm; 2e: R′ = Bz, OD-H, 30:1, 254 nm.

12

A typical procedure is as follows: A mixture of 2d (11.4 mmol), 2-propenyl acetate (34.3 mmol), and CAL-B (1.14 g, 0.1 g per mmol of 2d) in toluene (34 mL, 3 mL per mmol of 2d) was stirred at 50 °C for 48 h. The lipase was removed by filtration and the filtrate was concentrated to give crude solids. Purification by column chromatography (SiO2) afforded (3R,4S)-2d-OAc (5.58 mmol, 49%) and (3S,4R)-2d (5.59 mmol, 49%).

16

Methanolysis (K2CO3-MeOH, r.t., 40 min) provided the corresponding alcohol, which was analyzed by HPLC (Chiralcel OD-H, hexane-2-propanol = 20:1, 230 nm).