A Short Preparation of an Advanced Intermediate for Lactacystin Synthesis: The Complete Carbon Skeleton of Clasto-Lactacystin Dihydroxyacid

Abstract

An advanced intermediate 22 for lactacystin synthesis, containing the full carbon skeleton of the pyrrolidinone component, has been achieved in four steps from a protected glycine ester.

lactacystin - clasto-lactacystin - Dieckmann - acylation

References

1

Department of Chemistry, MARA University of Technology, 40450 Shah Alam, Selangor, Malaysia.

2 Omura S. Fujimoto T. Otogurro K. Matsuzaki K. Moriguchi R. Tanaka H. Sasaki Y. J. Antibiot.  1991,  44:  113 

3a Hefti F. Weinen WJ. Ann. Neurol.  1986,  20:  275 

3b Dohty P. Dickson JG. Flanigan TP. Walsh FS. J. Neurochem.  1985,  44:  1259 

4a Bogyo M. Wang EW. Curr. Top. Microbiol. Immunol.  2002,  268:  185 

4b Lee DH. Goldberg AL. Trends Cell Biol.  1998,  8:  397 

5a Fenteany G. Schreiber SL. J. Biol. Chem.  1998,  273:  8545 

5b Fenteany G. Standaert RF. Lane WS. Choi S. Corey EJ. Schreiber SL. Science  1995,  268:  726 

5c Craiu A. Gaczynska M. Akopian T. Gramm CF. Fenteany G. Goldberg AL. Rock KL. J. Biol. Chem.  1997,  272:  13437 

5d Fenteany G. Standaert RF. Reichard GA. Corey EJ. Schreiber SL. Proc. Natl. Acad. Sci. U.S.A.  1994,  91:  3358 

6a Corey EJ. Li W.-DZ. Nagamitsu T. Fenteany G. Tetrahedron  1999,  55:  3305 

6b Corey EJ. Reichard GA. Li W.-DZ. J. Am. Chem. Soc.  1998,  120:  2330 

6c Corey EJ. Li W.-DZ. Nagamitsu T. Angew. Chem. Int. Ed.  1998,  37:  1676 

6d Corey EJ. Li W.-DZ. Tetrahedron Lett.  1998,  39:  7475 

6e Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 

7a Chida N. Takeoka J. Ando K. Tsutsumi N. Ogawa S. Tetrahedron  1997,  53:  16287 

7b Chida N. Takeoka J. Tsutsumi N. Ogawa S. J. Chem. Soc., Chem. Commun.  1995,  793 

7c Nagamitsu T. Sunazuka T. Tanaka H. Omura S. Sprengeler PA. Smith AB. J. Am. Chem. Soc.  1996,  118:  3584 

7d Sunazuka T. Nagamitsu T. Matsuzaki K. Tanaka H. Omura S. Smith AB. J. Am. Chem. Soc.  1993,  115:  5302 

7e Uno H. Baldwin JE. Russell AT. J. Am. Chem. Soc.  1994,  116:  2139 

7f Kang SH. Jun H.-S. Chem. Commun.  1998,  1929 

7g Kang SH. Jun H.-S. Youn J.-H. Synlett  1998,  1045 

7h Iwama S. Gao W.-G. Shinada T. Ohfune Y. Synlett  2000,  1631 

7i Panek JS. Masse CE. Angew. Chem. Int. Ed.  1999,  38:  1093 

8a Masse CE. Morgan AJ. Adams J. Panek JS. Eur. J. Org. Chem.  2000,  2513 

8b Corey EJ. Li W.-D. Chem. Pharm. Bull.  1999,  47:  1 

9 Page PCB. Hamzah AS. Leach DC. Allin SM. Andrews DM. Rassias GA. Org. Lett.  2003,  353 

10 Kruijtzer JAW. Hofmeyer LJF. Heerma W. Versluis C. Liskamp RMJ. Chem.-Eur. J.  1998,  4:  1570 

11 Mander LN. Sethi SP. Tetrahedron Lett.  1983,  24:  5425 

12 Mukaiyama T. Bonno K. Naraska K. J. Am. Chem. Soc.  1974,  96:  7503 

13 Howard AS. Meerholz CA. Michael JP. Tetrahedron Lett.  1979,  20:  1339 

14 Katritzky AR. Pastor A. J. Org. Chem.  2000,  65:  3679 

15

Analytical data of compound 22: Colorless powder, 1:1 mixture of diastereoisomers, mp 109 °C. (Found: C, 69.26%; H, 5.98%; N, 3.10%. C₂₆H₂₇NO₆ requires C, 69.47%; H, 6.05%; N, 3.12%). IR(nujol): ν_max = 1778, 1748, 1698 cm^-1. [Found (M⁺): 449.18307. C₂₆H₂₇NO₆ requires 449.18384]. MS: m/z (%) = 449 (2) [M⁺], 394 (8), 314 (3), 91 (100), 65 (3). ¹H NMR (400 MHz, CDCl₃): δ = 1.48 (3 H, s), 1.59 (3 H, s), 1.69 (3 H, s, major), 1.72 (3 H, s, minor), 2.67 (3 H, s, major), 2.77-2.96 (4 H, m, major + minor), 3.11 (3 H, s, minor), 4.03 (1 H, d, J = 15.2 Hz, major), 4.18 (1 H, d, J = 15.2 Hz, minor), 4.51 (1 H, bs, minor), 4.56-4.57 (1 H, m, minor), 4.67 (1 H, br s, major), 4.97-4.98 (1 H, m, major), 5.06 (1 H, d, J = 12.4 Hz, minor), 5.14 (1 H, d, J = 12.4 Hz, major), 5.12-5.25 (1 H, m, minor), 5.12-5.25 (1 H, m, minor), 5.24 (1 H, d, J = 12.4 Hz, major), 5.36 (1 H, d, J = 15.2 Hz, major), 7.17-7.35. ¹³C NMR ( 100 MHz, CDCl₃): δ = 17.35 (major), 19.19 (minor), 23.73 (minor), 24.45 (major), 36.92 (major), 37.81 (minor), 44.47, 44.55, 52.19, 52.84 (OCH₃, minor), 57.59, 57.97, 68.11, 68.28, 76.11, 75.85, 118.21(minor), 118.78(major), 127.68, 127.94, 128.26, 128.29, 128.31, 128.48, 128.51, 128.53, 128.58, 128.63, 128.75, 129.08, 134.82, 135.15, 135.39, 137.83, 138.15, 164.84, 165.09, 166.72, 167.15, 170.62, 170.89, 199.95, 200.22.

16

Crystallographic data for 22 are available on request from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, fax: [phone], [e-mail], quoting the deposition number CCDC 206650.