Stereoselective Mn-mediated coupling of functionalized iodides and hydrazones: a synthetic entry to the tubulysin gamma-amino acids.
[structure: see text] Synthesis of gamma-amino acids, important building blocks in bioorganic and natural product chemistry, is accomplished using a stereoselective carbon-carbon bond construction of the chiral amine. Alkyl iodides and chiral hydrazones with protected alcohol functionality are coupled via highly diastereoselective photolytic Mn-mediated addition to the C=N bond, providing access to enantiomerically pure multifunctional chiral alpha-branched amines. Reductive N-N bond cleavage and alcohol oxidation provides alpha-substituted gamma-amino acid building blocks for tubulysin D.
Friestad
Gregory K
GK
Department of Chemistry, University of Vermont, Burlington, Vermont 05405, USA. gregory.friestad@uvm.edu
Marié
Jean-Charles
JC
Deveau
Amy M
AM
D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002384:Catalysis; D008345:Manganese / Q000737:chemistry*; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D000970:Antineoplastic Agents; D009842:Oligopeptides; D008345:Manganese