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US 6,849,743 B2Granted
Synthesis of clasto-lactacystin β-lactone and analogs thereof
AssigneeMillennium Pharmaceuticals, Inc.
InventorsFrançois Soucy, Louis Flamondon, Mark Behnke, William Roush
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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.
Claims2
A compound of Formula III:
- or a salt thereof wherein:
- R1 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkaryl, aralkyl, where the ring portion of any of said aryl, aralkyl, or alkaryl can be optionally substituted;
- R2 is alkyl, cycloalkyl, aryl, alkaryl, aralkyl, alkoxy, hydroxy, alkoxyalkyl, or amido, where the ring portion of any of said aryl, aralkyl, or alkaryl can be optionally substituted;
- R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkaryl, any of which can be optionally substituted;
- and
- R5 and R6 are independently one of alkyl or alkaryl;
- or R5 and R6 when taken together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring, which can be optionally substituted, and which can optionally include an additional oxygen or nitrogen atom.
4 more elements
Dependencies are inferred from the claim text.