PDF herunterladen
Synlett 2009(3): 417-420  
DOI: 10.1055/s-0028-1087541
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Cryptophycin-39 Unit A Precursor Synthesis by a Tandem Shi Epoxidation and Lactonization Reaction of trans-Styryl Acetic Acid

Benedikt Sammeta, Hanna Radzeya, Beate Neumannb, Hans-Georg Stammlerb, Norbert Sewald*a
a Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany
Fax: +49(521)106 8094; e-Mail: norbert.sewald@uni-bielefeld.de;
b Department of Chemistry, Inorganic Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany
Weitere Informationen

Publikationsverlauf

Received 13 October 2008
Publikationsdatum:
21. Januar 2009 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Unit A of cryptophycins is a δ-hydroxy acid with two or four stereogenic centers. The first synthesis of the unit A building block of cryptophycin-39 is based on a catalytic asymmetric Shi epoxidation of trans-styryl acetic acid followed by an in situ lactonization. The scope of this reaction has been investigated with respect to various β,γ-unsaturated carboxylic acids as substrates for the asymmetric synthesis of 4-hydroxy-5-phenyl-tetrahydrofuran-2-ones under Shi conditions.

Key words

asymmetric synthesis - bioorganic chemistry - epoxidations - lactones - natural products

    References and Notes

  • 1a Schwartz RE. Hirsch CF. Sesin DF. Flor JE. Chartrain M. Fromtling RE. Harris GH. Salvatore MJ. Liesch JM. Yudin K. J. Ind. Microbiol.  1990,  5:  113 
    Google Scholar
  • 1b Trimurtulu G. Ohtani I. Patterson GML. Moore RE. Corbett TH. Valeriote FA. Demchik L. J. Am. Chem. Soc.  1994,  116:  4729 
    Google Scholar
  • 1c Golakoti T. Ogino J. Heltzel CE. Husebo TL. Jensen CM. Larsen LK. Patterson GML. Moore RE. Mooberry SL. Corbett TH. Valeriote FA. J. Am. Chem. Soc.  1995,  117:  12030 
    Google Scholar
  • 1d Kobayashi M. Kurosu M. Ohyabu N. Wang W. Fujii S. Kitagawa I. Chem. Pharm. Bull.  1994,  42:  2196 
    Google Scholar
  • 1e Kobayashi M. Aoki S. Ohyabu N. Kurosu M. Wang W. Kitagawa I. Tetrahedron Lett.  1994,  35:  7969 
    Google Scholar
  • For reviews, see:
  • 1f Eißler S. Stončius A. Nahrwold M. Sewald N. Synthesis  2006,  3747 
    Google Scholar
  • 1g Eggen M. Georg GI. Med. Res. Rev.  2002,  22:  85 
    Google Scholar
  • 1h Tius MA. Tetrahedron  2002,  58:  4343 
    Google Scholar
  • 2a Al-awar RS. Corbett TH. Ray JE. Polin L. Kennedy JH. Wagner MM. Williams DC. Mol. Cancer Ther.  2004,  9:  1061 
    Google Scholar
  • 2b Smith CD. Zhang X. Mooberry SL. Patterson GM. Moore RE. Cancer Res.  1994,  54:  3779 
    Google Scholar
  • 3 Chaganty S. Golakoti T. Heltzel C. Moore RE. Yoshida WY. J. Nat. Prod.  2004,  67:  1403 
    CrossrefGoogle Scholar
  • 4a Gardinier KM. Leahy JW. J. Org. Chem.  1997,  62:  7098 
    Google Scholar
  • 4b Liang J. Moher ED. Moore RE. Hoard DW. J. Org. Chem.  2000,  65:  3143 
    Google Scholar
  • 4c Pousset C. Haddad M. Larchevêque M. Tetrahedron  2001,  57:  7163 
    Google Scholar
  • 4d Li L.-H. Tius MA. Org. Lett.  2002,  4:  1637 
    Google Scholar
  • 4e Mast CA. Eißler S. Stončius A. Stammler H.-G. Neumann B. Sewald N. Chem. Eur. J.  2005,  11:  4667 
    Google Scholar
  • 5 Eißler S. Nahrwold M. Neumann B. Stammler H.-G. Sewald N. Org. Lett.  2007,  9:  817 
    CrossrefGoogle Scholar
  • 6 Kino R. Daikai K. Kawanami T. Furuno H. Inanaga J. Org. Biomol. Chem.  2004,  2:  1822 
    CrossrefGoogle Scholar
  • 7 van Horn JD. Burrows CJ. Tetrahedron Lett.  1999,  40:  2069 
    CrossrefGoogle Scholar
  • 8a Wang ZX. Tu Y. Frohn M. Zhang JR. Shi Y.
    J. Am. Chem. Soc.  1997,  119:  11224 
    Google Scholar
  • 8b Wang ZX. Tu Y. Frohn M. Shi Y. J. Org. Chem.  1997,  62:  2328 
    Google Scholar
  • 8c Shi Y. Acc. Chem. Res.  2004,  37:  488 
    Google Scholar
  • 8d Wong OA. Shi Y. Chem. Rev.  2008,  108:  3958 
    Google Scholar
  • 9 Hoard DW. Moher ED. Martinelli MJ. Norman BH. Org. Lett.  2002,  4:  1813 
    CrossrefGoogle Scholar
  • 10 Ager DJ. Anderson K. Oblinger E. Shi Y. VanderRoest J. Org. Process Res. Dev.  2007,  11:  44 
    CrossrefGoogle Scholar
  • 13a

    Synthesis of (3 R ,4 R ,5 S )-4-Hydroxy-3-methyl-5-phenyl-tetrahydrofuran-2-one (6) Diisopropylamine (11.56 mmol, 1.6 mL) in THF (28 mL) was cooled to -78 ˚C, then n-BuLi (1.6 M in hexane, 11.49 mmol, 7.2 mL) was added dropwise over 15 min. The solution was stirred for 15 min at -78 ˚C and for 30 min at r.t. The LDA solution was cooled to -78 ˚C again and DMPU (34.87 mmol, 4.2 mL) was added. After 45 min lactone (5, 4.60 mmol, 819 mg) in THF (19.2 mL) was added during 90 min. After stirring for 45 min and addition of THF (16 mL), MeI (46.6 mmol, 2.9 mL) in THF (8.6 mL) was added during 150 min. The solution was stirred overnight at -78 ˚C. Acetic acid (0.6 mL) in THF (1.0 mL) was added, and the suspension was warmed to r.t. Then, 5% aq Na2SO3 soln (8.8 mL) was added, and after 5 min the solvent was removed in vacuo (40 ˚C), until a pink suspension remained, which was partitioned between Et2O (40 mL) and H2O (20 mL). The aqueous layer was extracted with Et2O (4 × 60 mL), and the combined organic phases were washed with 5% aq KHSO4 soln (30 mL) and brine (15 mL). After drying over Na2SO4 the solvent was removed in vacuo (40 ˚C), and the residue was purified by flash chromatography (hexane-EtOAc, 7:3). The product (3.80 mmol, 731 mg, 90% ee, 85% de) was recrystallized in EtOAc (1 mL) at -22 ˚C overnight. A colorless solid (6, 3.00 mmol, 576 mg, 65%, >99% ee, 92% de) was obtained; [α]D ²4 6.21 (c 1.18, CHCl3); mp 90 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 7.30-7.50 (m, 5 H), 5.06 (d, J = 7.5 Hz, 1 H), 3.98 (m, 1 H), 2.77 (dq, J = 9.4, 6.9 Hz, 1 H), 2.61 (d, J = 5.0 Hz, 1 H), 1.36 (d, J = 6.9 Hz, 3 H). ¹³C NMR (126 MHz, CDCl3): δ = 176.0, 136.6, 128.9, 128.8, 125.7, 84.2, 81.4, 43.6, 12.3. IR (neat): 3409, 3069, 3035, 2974, 2935, 2886, 1732, 1499, 1458, 1363, 1312, 1254, 1184, 1135, 1092, 971, 921, 854, 834, 765, 715, 695, 653 cm-¹. MS (EI): m/z = 192.1 [M+], 174.1 [M+ - H2O], 107.0 [Ph - CHOH+]. HRMS (EI): m/z calcd for C11H12O3 + [M+]: 192.07864; found: 192.07934. HPLC [Chiralpak AD, 2-PrOH-hexane (1:9), 1 mL/min]: t R = 13.4 min (6), 9.2 min (ent-6). Anal. Calcd (%) for C11H12O3: C, 68.74; H, 6.29. Found: C, 68.67; H, 6.24.

  • 13b Chen SY. Joullie MM.
    J. Org. Chem.  1984,  49:  2168 
    Google Scholar
  • 13c

    CCDC 703492 contains the crystallographic data of 6. They can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

  • 14 Harcken C. Brückner R. Synlett  2001,  718 
    Google Scholar
  • 15 Lee E. Jeong EJ. Kang EJ. Sung LT. Hong SK. J. Am. Chem. Soc.  2001,  123:  10131 
    CrossrefGoogle Scholar
  • 16 Tripathy NK. Georg GI. Tetrahedron Lett.  2004,  45:  5309 
    CrossrefGoogle Scholar
  • 18a

    Synthesis of (1 S ,2 R ,3 S ,4 S )-3-Methyl-1-phenylhept-6-ene-1,2,4-triol (11) A 5% aq HCl soln (4 mL) was added to a solution of homoallyl alcohol 9 (0.615 mmol, 170.0 mg) in MeOH (6 mL). After refluxing the solution for 90 min MeOH was removed in vacuo (40 ˚C), and the aqueous phase was extracted with Et2O (5 × 30 mL), dried over MgSO4, and purified by flash chromatography (hexane-EtOAc, 7:3). A colorless crystalline solid (11, 0.405 mmol, 95.7 mg, 66%) was obtained; [α]D ²4 43.59 (c 1.22, CHCl3); mp 77 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 7.26-7.49 (m, 5 H), 5.80 (m, 1 H), 5.13-5.20 (m, 2 H), 4.70 (δ, J = 7.5 Hz, 1 H), 4.15 (d, J = 7.5 Hz, 1 H), 3.70 (m, 1 H), 2.60 (d, J = 2.5 Hz, 1 H), 2.27-2.44 (m, 3 H), 2.21 (s, 1 H), 1.98 (m, 1 H), 1.16 (d, J = 6.9 Hz, 3 H). ¹³C NMR (126 MHz, CDCl3): δ = 141.8, 134.8, 128.6, 128.1, 126.8, 118.4, 75.1 75.0, 74.1, 40.0, 37.2, 11.2. IR (neat): 3545, 3345, 3063, 3030, 2970, 2923, 2360, 2341, 1639, 1493, 1455, 1431, 1404, 1382, 1340, 1269, 1212, 1135, 1071, 1023, 1000, 989, 974, 917, 870, 842, 786, 697, 639, 604, 544, 475, 419 cm-¹. ESI-MS: m/z = 259.2 [M + Na+]. ESI-HRMS: m/z calcd for C14H20O3Na+ [M + Na+] 259.13047; found: 259.13030. Anal. Calcd (%) for C14H20O3: C, 71.16; H, 8.53. Found: C, 71.00; H, 8.60.

  • 18b

    CCDC 703493 contains the crystallographic data of 11. They can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

11

Synthesis of (4 R ,5 S )-4-hydroxy-5-phenyl-tetrahydro-furan-2-one (5) trans-Styryl acetic acid (4, 21.8 mmol, 3.54 g) was dissolved in MeCN (210 mL). Aqueous KOH soln (1 M, 21.8 mmol, 21.8 mL), acetate buffer (150 mL, prepared by adding 5.00 mL AcOH to 13.82 g K2CO3 in 1000 mL H2O and pH adjusted to 9.3 by the dropwise addition of concd aq NaOH soln) and n-Bu4NHSO4 (0.954 mmol, 324 mg) were added. The solution was cooled to 0 ˚C and Shi catalyst (3, 7.16 mmol, 1.85 g) was added. Freshly prepared Oxone (29.90 mmol, 18.36 g) in aq Na2EDTA solution (0.4 mM, 0.0432 mmol, 108 mL) and aq K2CO3 soln (108 mL, prepared by dissolving 32.00 g K2CO3 in 200 mL H2O) were separately added within 120 min at 0 ˚C. The cooling bath was removed, and the mixture was stirred for 180 min. Aqueous HCl (6 M, 0.36 mol, 60 mL) was carefully added. The solution was extracted with Et2O (1 × 600 mL and 2 × 500 mL). The combined organic layers were washed with sat. aq NaHCO3 solution (200 mL) and brine (30 mL). After drying over Na2SO4 the solvent was removed in vacuo (40 ˚C) and the crude material was purified by flash chromatography (hexane-EtOAc 3:2) giving a crystalline solid (10.78 mmol, 1.920 g, 82% ee), which was recrystallized from EtOAc (3.5 mL) at 2 ˚C overnight yielding (4R,5S)-4-hydroxy-5-phenyl-tetrahydrofuran-2-one (5, 9.58 mmol, 1.708 g, 44%, 90% ee) as a colorless solid; [α]D ²4 2.57 (c 1.38, CHCl3). HPLC [Chiralpak AD, 2-PrOH-hexane (1:9), 1 mL/min]: t R = 16.6 min (5), 12.2 min (ent-5). Anal. Calcd (%) for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.39; H, 5.67. Further analytical data are in accordance with ref. 7.

12

General Procedure for the Synthesis of Substituted trans -Styryl Acetic Acids (Table 1, Entries 2 and 3)
KOt-Bu (13 mmol, 1.469 g) in THF (14 mL) was added to a solution of the substituted benzaldehyde (9 mmol) and
(2-carboxyethyl)triphenylphosphonium bromide (6 mmol, 2.494 g) in THF (12 mL) at 0 ˚C over 15 min. After stirring for additional 15 min at 0 ˚C and overnight at r.t., H2O (10 mL) and Et2O (50 mL) were added. The phases were acidified with 6 M aq HCl soln to pH 1 and separated. The aqueous phase was extracted with Et2O (50 mL). The combined organic phases were extracted with sat. aq NaHCO3 soln (2 × 60 mL). The sat. aq NaHCO3 phases were washed with EtOAc (3 × 90 mL), acidified with concd aq HCl to pH 1 and extracted with Et2O (2 × 75 mL). The organic extracts were washed with H2O (20 mL) and brine (10 mL). After drying over Na2SO4 the solvent was removed in vacuo (40 ˚C) yielding the corresponding substituted trans-styryl acetic acid in 70-74% yield.

17

Synthesis of (5 S ,6 S , E )- tert -Butyl-6-[(4 R ,5 S )-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-5-hydroxyhept-2-enoate (10)
Homoallyl alcohol 9 (0.615 mmol, 170 mg) in CH2Cl2 (0.85 mL) was added to a solution of Grubbs II catalyst (0.026 mmol, 22.1 mg) and tert-butylacrylate (0.513 mmol, 74.4 µL) in CH2Cl2 (3.4 mL). The solution was refluxed in the dark overnight. The solvent was removed in vacuo (30 ˚C), and the residue was purified by flash chromatography (hexane-EtOAc, 8:2) yielding 10 (0.369 mmol, 138.8 mg, 72%) as a colorless oil; [α]D ²4 -7.50 (c 1.10, CHCl3). ¹H NMR (500 MHz, CDCl3): δ = 7.28-7.40 (m, 5 H), 6.77 (m, 1 H), 5.80 (d, J = 15.7 Hz, 1 H), 5.38 (d, J = 7.5 Hz, 1 H), 4.70 (dd, J = 3.8, 7.5 Hz, 1 H), 3.50 (m, 1 H), 2.37 (m, 1 H), 2.22 (m, 1 H), 1.58-1.72 (m, 4 H), 1.41-1.56 (m, 12 H), 0.71 (d, J = 6.9 Hz, 3 H). ¹³C NMR (126 MHz, CDCl3): δ = 165.5, 144.0, 138.0, 128.2, 127.5, 126.6 125.7, 108.2, 80.3, 79.4, 78.1, 73.5, 38.3, 37.4, 28.2, 26.3 24.7, 11.2. IR (neat): 3453, 2979, 2934, 2360, 1709, 1651, 1494, 1454, 1379, 1367, 1326, 1253, 1210, 1086, 1044, 1029, 1006, 980, 917, 879, 850, 730, 700, 647, 512, 466 cm-¹. ESI-MS: m/z = 399.2 [M + Na+]. ESI-HRMS: m/z calcd for C22H32O5Na+ [M + Na+]: 399.21420; found: 399.21373.