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US 2004/0110982 A1Published application
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
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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.
Claims20
A method of making a compound of Formula I,
- 8
- 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,
- 9
- 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.
4 more elements
A method of making a compound of Formula IV,
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- or a corresponding stereoisomer having opposite stereochemistry of Formula IV, wherein R1 and R2 are N-terminal and C-terminal protecting groups, respectively, the method comprising:
- reacting a compound of Formula III,
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- or a corresponding stereoisomer having opposite stereochemistry of Formula III, with zinc to form an organozinc reagent;
- and
- reacting the organozinc reagent with hexafluoroacetone to yield the compound of Formula IV or the corresponding stereoisomer, wherein R1 and R2 in Formula III are as defined in Formula IV.
4 more elements
A method of making a compound represented by Formula I,
- 14
- 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,
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- or a corresponding stereoisomer having opposite stereochemistry of Formula II, with an iodinating agent to yield a compound of Formula III,
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- 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 reagent;
- reacting the organozinc reagent with hexafluoroacetone to form a compound having a tertiary hydroxy group as represented by Formula IV,
- 17
- or to form a corresponding stereoisomer having opposite stereochemistry of Formula IV;
- displacing the tertiary hydroxy group using 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.
9 more elements
A compound of Formula IV,
- 18
- or a corresponding stereoisomer having opposite stereochemistry of Formula IV, wherein R1 and R are, respectively, N-terminal and C-terminal protecting groups.
Dependencies are inferred from the claim text.