Synthesis of (S)-6-Hydroxytryptophan and Derivatives Thereof
AssigneeHeidelberg Pharma Research GmbH
InventorsWerner Simon, Susanne Werner-Simon, Christoph Müller
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Abstract
The present invention relates to novel methods and compounds for synthesizing amanitin derivatives. The invention in particular relates to methods for synthesizing (S)-6-hydroxy-tryptophan derivatives which can be used as building blocks for synthesizing amanitin derivatives or amatoxin drug conjugates. The invention further relates to intermediate compounds of said synthesis pathways for use in amanitin derivative and amatoxin drug conjugate synthesis, and to the use of particular catalysts suited for mediating said synthesis pathways.
Claims19
A method for synthesizing (S)-6-Acetyloxy-N-tert-butoxycarbonyl-tryptophan (HDP 30.2550) or (S)-6-hydroxytryptophan, wherein said method comprises at least one step of enantiomer-selective hydrogenation of an olefinic precursor compound by use of at least one chiral catalyst.
A compound selected from the group consisting of
A method of synthesizing amanitin, an amanitin derivative, or an amatoxin-drug conjugate, comprising use of a dehydroamino acid compound selected from the group consisting of compounds I, II, III, IV and V
- wherein
- R1 is selected from:
- H, alkyl, alkenyl, aryalkyl optional substituted,
- R2 is selected from:
- Boc, Cbz, N protecting groups,
- R3 is selected from:
- Boc, Cbz, N protecting groups, and
- R4 is an amino acid residue.
A method for catalyzing a hydrogenation reaction, comprising use of a compound selected from the group consisting of compound HDP 30.2758, (R,R)-Et-DUPHOS (BF4−), (R,R)-DuPhos-Ferrocene (BF4−), (R,R)-DuPhos-Ferrocene-Et2 (BF4−), (R,R)-DuPhos-Alkyl (CF3SO3−), and (R,R)-Phenyl-DuPhos-Alkyl (BF4−) as a catalyst for hydrogenation in the following reaction:
Dependencies are inferred from the claim text.