Abstract
Two distinct and scalable enantioselective approaches to the tricyclic indole (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate, an important synthon for a preclinical S1P(1) receptor agonist, are reported. Route 1 employs a modified version of Smith's modular 2-substituted indole synthesis as the key transformation. Route 2 involves a highly enantioselective CuH-catalyzed 1,4-hydrosilylation as the stereodefining step. Both routes can be performed without chromatography to provide multigram quantities of the tricycle in ≥98% ee.
MeSH terms
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Acetates / chemical synthesis*
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Acetates / chemistry
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Acetates / pharmacology
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Catalysis
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Fingolimod Hydrochloride
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Molecular Structure
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Propylene Glycols / chemical synthesis
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Propylene Glycols / chemistry
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Propylene Glycols / pharmacology
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology
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Receptors, Lysosphingolipid / agonists
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Sphingosine / analogs & derivatives
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Sphingosine / chemical synthesis
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Sphingosine / chemistry
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Sphingosine / pharmacology
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Stereoisomerism
Substances
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(R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo(1,2-a)indol-1-yl)acetate
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Acetates
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Indoles
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Propylene Glycols
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Pyrroles
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Receptors, Lysosphingolipid
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Fingolimod Hydrochloride
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Sphingosine