Synthesis of clasto-lactacystin β-lactone and analogs...

Details Synthesis of clasto-lactacystin β-lactone and analogs... Synthesis of clasto-lactacystin β-lactone and analogs...

2005-02-01

2005-02-01

Saeed, Kamal (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C560S103000, C560S155000

Reexamination Certificate

active

06849743

ABSTRACT:
The present invention is directed to an improved synthesis of clasto-lactacystin-β-lactone, and analogs thereof, that proceeds in fewer steps and in much greater overall yield than syntheses described in the prior art. The synthetic pathway relies upon a novel stereospecific synthesis of an oxazoline intermediate and a unique stereoselective addition of a formyl amide to the oxazoline. Also described are novel clasto-lactacystin-β-lactones, and analogs thereof and their use as proteasome inhibitors.

REFERENCES:
patent: 5831068 (1998-11-01), Nair et al.
patent: 5942494 (1999-08-01), Ginsberg et al.
patent: 6271199 (2001-08-01), Brand et al.
patent: WO 9632105 (1996-10-01), None
U.S. patent application Ser. No. 08/832,301, filed Apr. 3, 1997, Goldenberg et al.
Omura, et al., “Structure of Lactacystin, A New Microbial Metabolite Which Induces Differentiation of Neuroblastoma Cells,”J. Antibiotics, vol. 44(1), pp. 117-118 (1991).
Omura, et al., “Lactacystin, A Novel Microbial Metabolite, Induces Neuritogenesis of Neuroblastoma Cells,”J. Antibiotics, vol. 44(1), pp. 113-116 (1991).
Dick, et al., “Mechanistic Studies on the Inactivation of the Proteasome by Lactacystin,”J. Biol. Chem., vol. 271(13), pp. 7273-7276 (1996).
Haddad, et al., “Asymmetric Synthesis of the Abbott Amino Dihydroxyethylene Dipeptide Isostere Subunit,”Tetrahedron Lett..vol. 37(26), pp. 4525-4528 (1996).
Wang, et al., “Large-Scale and Highly Enantioselective Synthesis of the Taxol C-13 Side Chain through Asymmetric Dihydroxylation,”J. Org. Chem.vol. 59, pp. 5104-5105 (1994).
Choi, S., et al., “Total Syntheses of (6R)-Lactacystin and Beta-Lactone Derivatives,”Chpt. 3, Dissertation, Dept. of Chemistry, Harvard University(1995).
Chida, N. et al.,J. Chem. Soc., Chem. Comm., vol. 7(7), pp. 793-794 (1995).
Corey, et al.,J. Am. Chem. Soc., vol. 114(26), pp. 10677-10678 (1992).
Corey, et al.,Tetrahedron Letters., vol. 34(44), pp. 6969-6972 (1993).
Corey, et al.,Tetrahedron Letters., vol. 34(44), pp. 6973-6976 (1993).
Corey, et al.,Tetrahedron Letters., vol. 34(44), pp. 6977-6980 (1993).
Dikshit, et al.,Tetrahedron Letters., vol. 36(34), pp. 6131-6134 (1995).
Fenteany, et al.,Proc. Natl. Acad. Sci. USA, vol. 91, pp. 3358-3362 (1994).
Fenteany, et al.,Science, vol. 268, pp. 726-731 (1995).
Nagamitsu, et al.,J. Am. Chem. Soc., vol. 118, pp. 3584-3590 (1996).
Nakagawa, et al.,Tetrahedron Letters., vol. 35(28), pp. 5009-5012 (1994).
Sunazuka, et al.,J. Am. Chem. Soc., vol. 115, pp. 5302 (1993).
Uno, et al.,J. Am. Chem. Soc., vol. 116, pp. 2139-2140 (1994).
WPI Derwent Accession No. 96-485455, English Abstract of WO 96/32105 (1996).
Shibata, et al.,Tetrahedron Letters., vol. 37, pp. 2791-2794 (1996).
Wipf, et al.,Tetrahedron Letters., vol. 37, pp. 4659-4662 (1996).

Affiliated with

Also associated with

Rating

Synthesis of clasto-lactacystin β-lactone and analogs... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Synthesis of clasto-lactacystin β-lactone and analogs..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthesis of clasto-lactacystin β-lactone and analogs... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3487791