Back to results
US 6,787,664 B2Granted
Process for preparing single enantiomers of 5,5,5,5′,5′,5′-hexafluoroleucine and protected analogs
AssigneesWarner-Lambert Company, The Regents of the University of Michigan
InventorsJames T. Anderson, Edward Neil Marsh, Peter Laurence Toogood
Life of this patent
Estimating the term…
Abstract
A process for synthesizing L and D-5,5,5,5′,5′,5′-hexafluoroleucine and protected analogs is disclosed. These compounds have utility in the preparation of fluorous peptides and proteins, which display interesting and unusual properties including strong self-association and an affinity for lipid bilayers.
Claims14
A method of making a compound of Formula I,
- or a corresponding stereoisomer having opposite stereochemistry of Formula I, wherein R1 and R2 are N-terminal and C-terminal protecting groups, respectively, the method comprising:
- providing a compound having a tertiary hydroxy group as represented by Formula IV,
- or providing a corresponding stereoisomer having opposite stereochemistry of Formula IV, wherein R1 and R2 in Formula IV are as defined in Formula I;
- and
- displacing the tertiary hydroxy group to yield the compound of Formula I or the corresponding stereoisomer.
2 more elements
A method of making a compound represented by Formula I,
- or a corresponding stereoisomer having opposite stereochemistry of Formula I, wherein R1 and R2 are N-terminal and C-terminal protecting groups, respectively, the method comprising:
- reacting a compound of Formula II,
- or a corresponding stereoisomer having opposite stereochemistry of Formula II, with an iodinating agent to yield a compound of Formula III,
- or a corresponding stereoisomer having opposite stereochemistry of Formula III;
- reacting the compound of Formula III or the corresponding stereoisomer with zinc to form an organozinc derivative of Formula III;
- reacting the organozinc reagent with hexafluoroacetone to form a compound having a tertiary hydroxy group as represented by Formula IV,
- or to form a corresponding stereoisomer having opposite stereochemistry of Formula IV;
- displacing the tertiary hydroxy group by radical deoxygenation to yield the compound of Formula I or the corresponding stereoisomer, wherein R1 and R2 in Formula II, Formula III, and Formula IV are as defined in Formula I.
5 more elements
Dependencies are inferred from the claim text.