D.F. Taber, P. Gu / Tetrahedron 65 (2009) 5904–5907
5907
(ddd, 1H, J¼1.2, 7.2, and 18.4 Hz), 2.31–2.43 (m, 3H), 2.26 (t, 3H,
J¼7.6 Hz), 2.16 (dd, 1H, J¼8.8 and 18.4 Hz), 1.98–2.03 (m, 4H), 1.85–
1.89 (m,1H),1.75–1.78 (m, 1H),1.57–1.65 (m, 4H),1.28–1.40 (m, 2H),
71.5, 54.3, 53.0; IR (film): 3464, 2928,1733,1453,1163 cmꢀ1; HRMS:
calcd for C30H34O7Na 529.2202, found 529.2198.
1.20–1.24 (m, 6H), 0.84 (s, 9H), 0.01 (s, 6H); 13C NMR
d u: 214.5,
4.7. (1,2,3,4-Tetranor)-9,15-dioxo-11-hydroxy-13,14-
dihydroprostanedioic acid (PGE2UM) 2
173.4, 173.0, 170.2, 60.3, 60.2, 47.1, 34.11, 34.06, 24.73, 24.70, 23.3,
18.0; d: 133.1, 131.7, 72.7, 72.5, 54.5, 52.6, 25.7 (3), 21,2, 14.24, 14.21,
ꢀ4.7, ꢀ4.8; IR (film) 2935, 1735,1373, 1240, 840 cmꢀ1; ESI MS (m/z),
563.3 (MþþNa); HRMS: calcd for C28H48O8SiNa 563.3016, found
563.3012.
To a stirred solution of enone 25 (4.3 mg, 0.0085 mmol) in
ethanol (1 mL) was added Pd–C (40 mg). A H2 balloon was attached,
and the mixture was stirred at rt for 40 min. The reaction mixture
was filtered and concentrated to give the desired PGE2UM 2 (2.5 mg,
90% yield from the enone 25); TLC Rf (Et2O/0.5 M pH¼4 aqueous
4.5. Dibenzyl (1,2,3,4-tetranor)-9,15-dioxo-11-dimethyl-
(dimethylethyl)silyloxyprostanedioate 24
buffer/HOAc¼90/9/1)¼0.14; [
a
]
ꢀ9.1 (c 0.10, MeOH); 1H NMR
D
(CD3OD)
d
3.98 (q, 1H, J¼6.4 Hz), 2.57–2.67 (m, 3H), 2.46–2.48 (m,
2H), 2.32–2.40 (m, 2H), 2.23 (br s, 2H), 2.08 (dd, 1H, J¼18.0 and
To stirred solution of acetate R-5 (21.2 mg, 0.039 mmol) in eth-
anol (1 mL) was added NaBH4 (2.2 mg). After an additional 40 min,
the reaction mixture was partitioned between EtOAc and H2O. The
organic extract was dried (Na2SO4) and concentrated to afford the
crude mixture of diastereomeric alcohols.
6.8 Hz), 1.70–1.84 (m, 5H), 1.55–1.59 (m, 5H); 13C NMR
d
u: 217.4,
211.6, 176.3,175.9, 45.9, 41.4, 38.9, 33.4, 26.9, 25.7, 25.1, 23.9; d: 71.5,
52.0, 47.9; IR (film): 3441, 1703, 1406 cmꢀ1; HRMS: calcd for
C16H24O7Na 351.1420, found 351.1414.
To a stirred solution of the crude diols in THF (1 mL) was added
a 1 M solution of aqueous LiOH (1 mL, 1 mmol) at room tempera-
ture. After stirring for 24 h, the mixture was acidified with 1 M
aqueous HCl to pH¼3–4, and partitioned between CHCl3 and sat-
urated brine. The organic extract was dried (Na2SO4) and concen-
trated to afford the bisacid crude 22.
Acknowledgements
We thank the National Institutes of Health (GM42056) for
support of this work. We thank Dr. John Dykins for mass spectro-
metric measurements, supported by the NSF (0541775), and Dr.
Glenn Yap for X-ray analysis. This work is dedicated to the memory
of our friend and colleague Jason D. Morrow.
The crude diacid 22 was dissolved in DMF (1 mL), then pow-
dered K2CO3 (39 mg, 0.28 mmol) and benzyl bromide (48 mg,
0.14 mmol) were added. After stirring for 24 h, the reaction mixture
was partitioned between EtOAc and H2O. The organic extract was
dried (Na2SO4) and concentrated, and the residue was chromato-
graphed to afford the bisbenzyl ester 23 (12.1 mg, 50% yield for
three steps from the acetate R-5); TLC Rf (MTBE/petroleum
ether¼1/1)¼0.28 and 0.19; 1H NMR (diastereomeric mixture, typ-
Supplementary data
General experimental procedures, experimental procedures,
and spectra for all new compounds. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
ical signal peaks were recorded)
2H), 5.10–5.11 (m, 4H), 3.94–4.04 (m, 3H).
To stirred solution of the bisbenzyl ester 23 (12.1 mg,
d 7.31–7.36 (m, 10H), 5.30–5.53 (m,
References and notes
a
0.019 mmol) in CH2Cl2 (1 mL) was added Dess–Martin periodinane
(33 mg, 0.078 mmol) at room temperature. After an additional
30 min, the mixture was concentrated and the residue was chro-
matographed to afford the desired enone 24 (9.5 mg, 40% yield from
1. For an overview of the physiological function of PGE2, see: (a) Craven, P. A.; Ver-
balis, J. G.; DeRubertis, F. R. Kidney Int.1986, 29,1110; (b) Tchetina, E. V.; Di Battista,
J. A.; Zukor, D. J.; Antoniou, J.; Poole, A. R. Arthritis Res. Ther. 2007, 9, R75; (c) Ma, W.;
Quirion, R. Neurosci. Lett. 2008, 437, 165.
2. For leading references to the elevated levels of PGE2 observed with some lung
cancers, see (a) Huang, M.; Stolina, M.; Sharma, S.; Mao, J. T.; Zhu, L.; Miller, P. W.;
Wollman, J.; Herschmann, H.; Dubinett, S. M. Cancer Res. 1998, 58, 1208; (b)
Dohadwala, M.; Batra, R. K.; Luo, J.; Lin, Y.; Krysan, K.; Po˜ld, M.; Sharma, S.;
Dubinett, S. M. J. Biol. Chem. 2002, 277, 50828; (c) Murphey, L. J.; Williams, M. K.;
Sanchez, S. C.; Byrne, L. M.; Csiki, J. A.; Oates, J. A.; Johnson, D. H.; Morrow, J. D.
Anal. Biochem. 2004, 334, 266.
3. (a) We recently reported a synthesis of the diethyl ester 3: Taber, D. F.; Teng, D.
J. Org. Chem. 2002, 67, 1607; This synthesis was based on an approach to the
prostaglandins and isoprostanes that we had previously reported: (b) Taber,
D. F.; Hoerrner, R. S. J. Org. Chem. 1992, 57, 441; (c) Taber, D. F.; Herr, R. J.;
Gleave, D. M. J. Org. Chem. 1997, 62, 194; (d) Taber, D. F.; Xu, M.; Hartnett, J. C.
J. Am. Chem. Soc. 2002, 124, 13121.
R-5); TLC Rf (MTBE/petroleum ether¼1/1)¼0.77; [
a
]
D ꢀ34.7 (c 0.45,
CH2Cl2); 1H NMR
d
7.31–7.37 (m, 10H), 6.69 (dd, 1H, J¼15.6 and
8.8 Hz), 5.11 (s, 2H), 5.09 (s, 2H), 4.09 (q,1H, J¼8.4 Hz), 2.67 (ddd,1H,
J¼0.8, 7.2, and 18.4 Hz), 2.44–2.57 (m, 5H), 2.47–2.49 (m, 2H), 2.14–
2.28 (m, 2H),1.78–1.96 (m, 2H),1.65–1.67 (m, 4H), 0.85 (s, 9H), 0.02 (s,
3H), 0.00 (s, 3H); 13C NMR
d u:213.5,198.9,173.2,172.7,135.9 (2), 66.3,
66.2, 47.1, 40.3, 34.1, 31.4, 24.5, 23.4, 23.3, 18.0; d: 144.8, 132.2, 128.6
(4), 128.3 (3), 128.22 (2), 128.20, 72.2, 54.5, 52.4, 25.6 (3), ꢀ4.65,
ꢀ4.74; IR (film): 2932,1738,1162, 838, 744 cmꢀ1; ESI MS (m/z), 643.2
(MþþNa); HRMS: calcd for C36H48O7SiNa 643.3067, found 643.3056.
4. For R-selective acetylation of allylic alcohols with Amano lipase AK, see: Taber,
D. F.; Reddy, G. P.; Arneson, K. O. J. Org. Chem. 2008, 73, 3467.
5. (a) For selective diazo transfer to a-benzoyl ketones, see Taber, D. F.; Gleave, D.
4.6. Dibenzyl (1,2,3,4-tetranor)-9,15-dioxo-11-
hydroxyprostanedioate 25
M.; Moody, K.; Hennessy, M. J. J. Org. Chem. 1995, 60, 2283; (b) Taber, D. F.; Herr,
R. J.; Pack, S. K.; Geremia, J. M. J. Org. Chem. 1996, 61, 2908; (c) Taber, D. F.; Kong,
S.; Malcolm, S. C. J. Org. Chem. 1998, 63, 7953.
6. For the unsymmetrical ozonolysis of alkenes, see (a) Schreiber, S. L.; Claus, R. E.;
Reagen, J. Tetrahedron Lett. 1982, 23, 3867; (b) Taber, D. F.; Nakajima, K. J. Org.
Chem. 2001, 66, 3426.
7. (a) Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc.
1968, 90, 4869; (b) Tang, R.; Mislow, K. J. Am. Chem. Soc. 1970, 92, 2100; (c)
Evans, D. A.; Andrews, G. C.; Sims, C. L. J. Am. Chem. Soc. 1971, 93, 4956; (d)
Taber, D. F. J. Am. Chem. Soc. 1977, 99, 3513.
To a stirred solution of enone 24 (9.5 mg, 0.015 mmol) in CH3CN
(1 mL) at 0 ꢁC were added pyridine (0.1 mL) and 52% solution of HF
in H2O (0.2 mL). After stirring for 7 h, the reaction mixture was
mixed with silica gel, concentrated, and the residue was chroma-
tographed to afford the free enone 25 (6.5 mg, 84% yield from the
8. (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155; (b) Ireland, R. E.; Liu, L.
J. Org. Chem. 1993, 58, 2899.
enone 24); TLC Rf (MTBE/petroleum ether¼4/1)¼0.27; [
a
]
D þ11.2 (c
0.25, CH2Cl2); 1H NMR
d
7.31–7.38 (m, 10H), 6.72 (dd, 1H, J¼8.4 and
9. Three previous syntheses of 2 had been reported: (a) Boot, J. R.; Foulis, M. J.;
Gutteridge, N. J. A.; Smith, C. W. Prostaglandins 1974, 8, 439; (b) Taub, D.; Ze-
lawski, Z. S.; Wendler, N. L. Tetrahedron Lett. 1975, 16, 3667; (c) Lin, C. H. J. Org.
Chem. 1976, 41, 4045.
15.6 Hz), 6.31 (d, 1H, J¼15.6 Hz), 5.11 (s, 2H), 5.09 (s, 2H), 4.19 (q,
J¼8.4 Hz), 2.79 (ddd, J¼0.8, 7.2, and 18.4 Hz), 2.44–2.60 (m, 5H),
2.20–2.41 (4H), 1.81–1.97 (m, 2H), 1.65–1.68 (m, 5H); 13C NMR
d u:
10. 13C multiplicities were determined with the aid of a JVERT pulse sequence,
differentiating the signals for methyl and methine carbons as ‘d’ and for
methylene and quaternary carbons as ‘u’.
212.8, 199.2, 173.4, 172.7, 135.9, 135.8, 66.4, 66.3, 46.0, 40.5, 33.9,
31.3, 24.3, 23.4, 23.2; d: 144.2, 132.4, 128.6 (4), 128.3 (3), 128.2 (3),