LETTER
d-Formyl-d-valerolactone Precursor of Statin Side Chain
1147
(14) Beck, G.; Kesseler, K.; Baader, E.; Bartmann, W.;
heterocyclic phosphonium ylides are highly encouraging
and will be presented in due course.
Bergmann, A.; Granzer, E.; Jendralla, H.; Von Kerekjarto,
B.; Krause, R.; Paulus, E.; Schubert, W.; Wess, G. J. Med.
Chem. 1990, 33, 52.
(15) Časar, Z. Synlett 2008, 2036.
Acknowledgment
(16) Greenberg, W.; Varvak, A.; Hanson, S. R.; Wong, K.;
Huang, H.; Chen, P.; Burk, M. J. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5788.
(17) (a) Rosen, T.; Taschner, M. J.; Heathcock, C. H. J. Org.
Chem. 1984, 49, 3994. (b) Tang, J.; Brackenridge, I.;
Roberts, S. M.; Beecher, J.; Willetts, A. J. Tetrahedron
1995, 51, 13217. (c) Ghorpade, S. R.; Kalkote, U. R.;
Chavan, S. P.; Bhide, S. R.; Ravindranathan, T.; Puranik,
V. G. J. Org. Chem. 2001, 66, 6803.
The authors gratefully acknowledge Mr. P. Drnovšek for support of
this project, Dr. Bogdan Kralj, Dr. Dušan Žigon (Mass Spectrome-
try Center, Jožef Stefan Institute, Ljubljana, Slovenia), and Dr. M.
Vodopivec for mass spectral measurements, Mr. S. Borišek for ac-
quisition of NMR spectra, as well as Mr. M. Steinbücher (BSc) and
Mrs. J. Anžel (Dipl.-Ing.) for their contributions in some experi-
mental work.
(18) Tararov, V. I.; Andrushko, N.; Andrushko, V.; König, G.;
Spannenberg, A.; Börner, A. Eur. J. Org. Chem. 2006, 5543.
(19) Gillard, F.; Heissler, D.; Riehl, J.-J. J. Chem. Soc., Perkin
Trans. 1 1988, 2291.
(20) For example, see: (a) Coutrot, P.; Grison, C.; Bomont, C.
J. Organomet. Chem. 1999, 586, 208. (b)Corey, E.J.;Pyne,
S. G.; Su, W. Tetrahedron Lett. 1983, 24, 4883.
References and Notes
(1) (a) Endo, A.; Hasumi, K. Nat. Prod. Rep. 1993, 10, 541.
(b) Tobert, J. A. Nat. Rev. Drug Discovery 2003, 2, 517.
(c) Lahera, V.; Goicoechea, M.; de Vinuesa, S. G.; Miana,
M.; de las Heras, N.; Cachofeiro, V.; Luno, J. Curr. Med.
Chem. 2007, 14, 243.
(21) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) For recent review on hypervalent iodine reagents for the
oxidation of alcohols, see: Tohma, H.; Kita, Y. Adv. Synth.
Catal. 2004, 346, 111.
(2) Istvan, E. S.; Deisenhofer, J. Science 2001, 292, 1160.
(3) Endo, A.; Kuroda, M.; Tsujita, Y. J. Antibiot. 1976, 29,
1346.
(4) Also known as mevinolin, with a brand name of Mevacor®
(Merck & Co). For selected literature, see: (a) Endo, A.
J. Antibiot. 1979, 32, 852. (b) Alberts, A. W.; Chen, J.;
Kuron, G.; Hunt, V.; Huff, J.; Hoffman, C.; Rothrock, J.;
Lopez, M.; Joshua, H.; Harris, E.; Patchett, A.; Monaghan,
R.; Currie, S.; Stapley, E.; Albers-Schonberg, G.; Hensens,
O.; Hirshfield, J.; Hoogsteen, K.; Liesch, J.; Springer, J.
Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 3957.
(22) Synthesis of (4R,6S)-4-(tert-Butyldimethylsilyloxy)-6-
(dihydroxymethyl)tetrahydro-2H-pyran-2-one (4)
A mixture of 215 (500 mg, 1.92 mmol) and DMP (896 mg,
2.11 mmol) in CH2Cl2 (50 mL) was stirred at 26 °C for 30
min. The mixture was diluted with MTBE (35 mL) and
washed with sat. NaHCO3 (45 mL). The organic phase was
separated. The water phase was additionally extracted with
MTBE (3 × 25 mL). Combined organic layers were washed
with sat. aq Na2S2O3 (2 × 25 mL), sat. NaHCO3 (2 × 25 mL),
H2O (70 mL), dried (MgSO4), and concentrated under
reduced pressure to give pure hydrate 4 (498 mg, 94%) as a
white crystalline powder; mp 73–75 °C. 1H NMR (300
MHz, THF-d8): d = 0.10 (s, 6 H, CH3Si), 0.91 (s, 9 H,
CH3C), 1.80–2.00 (m, 2 H, H-5), 2.39 (dd, J = 17.1, 3.9 Hz,
1 H, H-3), 2.58 (dd, J = 17.1, 4.2 Hz, 1 H, H-3), 4.35–4.45
(m, 2 H, H-4, H-6), 4.83–4.91 [m, 1 H, CH(OH)], 5.14 (d,
(5) FDA approved in 1996, also known as eptastatin with a
brand name of Pravachol® (Bristol–Myers Squibb). See:
Tsujita, Y.; Kuroda, M.; Shimada, Y.; Tanzawa, K.; Arai,
M.; Kaneko, I.; Tanaka, M.; Masuda, H.; Tarumi, C.;
Watanabe, Y. Biochim. Biophys. Acta 1986, 877, 50.
(6) Also known as velostatin, with a brand name of Zocor®
(Merck & Co). For selected literature, see: Hoffman, W. F.;
Alberts, A. W.; Anderson, P. S.; Chen, J. S.; Smith, R. L.;
Willard, A. K. J. Med. Chem. 1986, 29, 849.
J = 6.0 Hz, 1 H, OH), 5.22 (d, J = 6.0 Hz, 1 H, OH). 13
C
(7) FDA approved in 1996, with a brand name of Lipitor®
[Pfizer (Parke–Davis)]. For selected literature, see: Roth,
B. D.; Blankley, C. J.; Chucholowski, A. W.; Ferguson, E.;
Hoefle, M. L.; Ortwine, D. F.; Newton, R. S.; Sekerke, C. S.;
Sliskovic, D. R.; Stratton, C. D.; Wilson, M. J. Med. Chem.
1991, 34, 357.
NMR (75 MHz, THF-d8): d = –4.79 (CH3Si), –4.74 (CH3Si),
18.7 (CCH3), 26.2 (CH3C), 31.0 (C-5), 40.4 (C-3), 65.1
(C-4), 79.1 (C-6), 91.7 [CH(OH)], 168.8 (C-2). IR (KBr):
n = 1697 cm–1. MS (ES+): m/z (%) = 851.6 (10) [3 M + Na]+,
575.4 (58) [2 M + Na]+, 570.4 (13) [2 M + NH4]+, 299.2 (35)
[M + Na]+, 294.2 (100) [M + NH4]+, 277.2 (88) [M + 1]+,
259.2 (73), 145.1 (8). Anal. Calcd (%) for C12H24O5Si: C,
52.14; H, 8.75. Found: C, 52.45; H, 9.18.
(8) FDA approved in 2003, with a brand name of Crestor®
(AstraZeneca). For selected literature, see: Watanabe, M.;
Koike, H.; Ishiba, T.; Okada, T.; Sea, S.; Hirai, K. Bioorg.
Med. Chem. 1997, 5, 437.
(23) Kralj, B.; Žigon, D.; Košmrlj, J.; Polanc, S. Rapid Commun.
Mass Spectrom. 1997, 11, 335.
(24) (a) Wu, J.; Serianni, A. S. Carbohydr. Res. 1991, 210, 51.
(b) McAlpine, J. M.; Riggs, N. V. Aust. J. Chem. 1975, 28,
211.
(25) (4R,6S)-4-(tert-Butyldimethylsilyloxy)-6,7-dihydroxy-
oxepan-2-one (5)
(9) FDA approved in 1993, with a brand name of Lescol®
(Novartis Pharma AG). For selected literature, see:
Fuenfschilling, P. C.; Pascale, H.; Mutz, J.-P. Org. Process
Res. Dev. 2007, 11, 13; and references cited therein.
(10) For selected literature, see: Suzuki, M.; Iwasaki, H.;
Fujikawa, Y.; Kitahara, M.; Sakashita, M.; Sakoda, R.
Bioorg. Med. Chem. 2001, 9, 2727.
Hydrate 4 (50 mg, 0.18 mmol) was dissolved in MeOH (2
mL) and left to stand at r.t. for 2.5 d. The solvent was
evaporated to dryness to give 5 (50 mg, 100%) as a colorless
solid. 1H NMR (300 MHz, CD3OD): d = 0.14 (s, 6 H,
CH3Si), 0.94 (s, 9 H, CH3C), 1.87–2.06 (m, 2 H, H-5), 2.52
(ddd, J = 17.5, 2.9, 2.0 Hz, 1 H, H-3), 2.72 (dd, J = 17.5, 3.8
Hz, 1 H, H-3), 4.42–4.52 (m, 1 H, H-4), 4.56–4.70 (m, 2 H,
H-6, H-7). 13C NMR (75 MHz, CD3OD): d = –4.82 (CH3Si),
–4.76 (CH3Si), 18.9 (CH3C), 26.2 (CH3C), 30.7 (C-5), 31.0
(C-5), 40.5 (C-3), 64.9 (C-4), 79.0, 79.5, 98.6, 98.8, 172.58
(11) Sit, S. Y.; Parker, R. A.; Motoc, I.; Han, W.;
Balasubramanian, N.; Catt, J. D.; Brown, P. J.; Harte, W. E.;
Thompson, M. D.; Wright, J. J. J. Med. Chem. 1990, 33,
2982.
(12) (a) Choi, H.; Shin, H. Synlett 2008, 1523. (b) Rádl, S.
Synth. Commun. 2003, 33, 2275. (c) Bode, S. E.; Wolberg,
M.; Müller, M. Synthesis 2006, 557; and references therein.
(13) Cardani, S.; Scolastico, C.; Villa, R. Tetrahedron 1990, 46,
7283.
Synlett 2009, No. 7, 1144–1148 © Thieme Stuttgart · New York