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

<A NAME="RD07003ST-1">1</A>

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

<A NAME="RD07003ST-2">2</A> Omura S. Fujimoto T. Otogurro K. Matsuzaki K. Moriguchi R. Tanaka H. Sasaki Y. J. Antibiot.  1991,  44:  113 

<A NAME="RD07003ST-3A">3a</A> Hefti F. Weinen WJ. Ann. Neurol.  1986,  20:  275 

<A NAME="RD07003ST-3B">3b</A> Dohty P. Dickson JG. Flanigan TP. Walsh FS. J. Neurochem.  1985,  44:  1259 

<A NAME="RD07003ST-4A">4a</A> Bogyo M. Wang EW. Curr. Top. Microbiol. Immunol.  2002,  268:  185 

<A NAME="RD07003ST-4B">4b</A> Lee DH. Goldberg AL. Trends Cell Biol.  1998,  8:  397 

<A NAME="RD07003ST-5A">5a</A> Fenteany G. Schreiber SL. J. Biol. Chem.  1998,  273:  8545 

<A NAME="RD07003ST-5B">5b</A> Fenteany G. Standaert RF. Lane WS. Choi S. Corey EJ. Schreiber SL. Science  1995,  268:  726 

<A NAME="RD07003ST-5C">5c</A> Craiu A. Gaczynska M. Akopian T. Gramm CF. Fenteany G. Goldberg AL. Rock KL. J. Biol. Chem.  1997,  272:  13437 

<A NAME="RD07003ST-5D">5d</A> Fenteany G. Standaert RF. Reichard GA. Corey EJ. Schreiber SL. Proc. Natl. Acad. Sci. U.S.A.  1994,  91:  3358 

<A NAME="RD07003ST-6A">6a</A> Corey EJ. Li W.-DZ. Nagamitsu T. Fenteany G. Tetrahedron  1999,  55:  3305 

<A NAME="RD07003ST-6B">6b</A> Corey EJ. Reichard GA. Li W.-DZ. J. Am. Chem. Soc.  1998,  120:  2330 

<A NAME="RD07003ST-6C">6c</A> Corey EJ. Li W.-DZ. Nagamitsu T. Angew. Chem. Int. Ed.  1998,  37:  1676 

<A NAME="RD07003ST-6D">6d</A> Corey EJ. Li W.-DZ. Tetrahedron Lett.  1998,  39:  7475 

<A NAME="RD07003ST-6E">6e</A> Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 

<A NAME="RD07003ST-7A">7a</A> Chida N. Takeoka J. Ando K. Tsutsumi N. Ogawa S. Tetrahedron  1997,  53:  16287 

<A NAME="RD07003ST-7B">7b</A> Chida N. Takeoka J. Tsutsumi N. Ogawa S. J. Chem. Soc., Chem. Commun.  1995,  793 

<A NAME="RD07003ST-7C">7c</A> Nagamitsu T. Sunazuka T. Tanaka H. Omura S. Sprengeler PA. Smith AB. J. Am. Chem. Soc.  1996,  118:  3584 

<A NAME="RD07003ST-7D">7d</A> Sunazuka T. Nagamitsu T. Matsuzaki K. Tanaka H. Omura S. Smith AB. J. Am. Chem. Soc.  1993,  115:  5302 

<A NAME="RD07003ST-7E">7e</A> Uno H. Baldwin JE. Russell AT. J. Am. Chem. Soc.  1994,  116:  2139 

<A NAME="RD07003ST-7F">7f</A> Kang SH. Jun H.-S. Chem. Commun.  1998,  1929 

<A NAME="RD07003ST-7G">7g</A> Kang SH. Jun H.-S. Youn J.-H. Synlett  1998,  1045 

<A NAME="RD07003ST-7H">7h</A> Iwama S. Gao W.-G. Shinada T. Ohfune Y. Synlett  2000,  1631 

<A NAME="RD07003ST-7I">7i</A> Panek JS. Masse CE. Angew. Chem. Int. Ed.  1999,  38:  1093 

<A NAME="RD07003ST-8A">8a</A> Masse CE. Morgan AJ. Adams J. Panek JS. Eur. J. Org. Chem.  2000,  2513 

<A NAME="RD07003ST-8B">8b</A> Corey EJ. Li W.-D. Chem. Pharm. Bull.  1999,  47:  1 

<A NAME="RD07003ST-9">9</A> Page PCB. Hamzah AS. Leach DC. Allin SM. Andrews DM. Rassias GA. Org. Lett.  2003,  353 

<A NAME="RD07003ST-10">10</A> Kruijtzer JAW. Hofmeyer LJF. Heerma W. Versluis C. Liskamp RMJ. Chem.-Eur. J.  1998,  4:  1570 

<A NAME="RD07003ST-11">11</A> Mander LN. Sethi SP. Tetrahedron Lett.  1983,  24:  5425 

<A NAME="RD07003ST-12">12</A> Mukaiyama T. Bonno K. Naraska K. J. Am. Chem. Soc.  1974,  96:  7503 

<A NAME="RD07003ST-13">13</A> Howard AS. Meerholz CA. Michael JP. Tetrahedron Lett.  1979,  20:  1339 

<A NAME="RD07003ST-14">14</A> Katritzky AR. Pastor A. J. Org. Chem.  2000,  65:  3679 

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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.

<A NAME="RD07003ST-16">16</A>

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.