Enantioselective Synthesis and Photoreactivity of a Diazirinyl-substituted (R)-β-Phenylalanine

Abstract

The first enantioselective synthesis of a photoreactive (R)-β -phenylalanine is described. In the key step, m-diazirinyl-substituted benzaldehyde is converted to a chiral sulfinimine in a Ti(OEt) 4mediated reaction, followed by diastereoselective enolate addition. The absolute configuration of photo (R)-β -phenylalanine was confirmed by Mosher analysis. The photo amino acid proved to be thermally stable under standard laboratory conditions. Irradiation in toluene afforded cycloheptatriene/norcaradiene valence tautomers, together with carbene benzylation. Quantumchemical calculations indicate a small triplet-singlet gap.

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

“…A photoreactive derivative of the cytotoxic jasplakinolides, geodiamolides [4–5], or seragamides ( 2 – 6 , seragamides A–E) [6] could also enable the search for additional targets in the cell, including proteins involved in transport or even membrane components. For this purpose, the 2-bromoabrine unit of 1 could be replaced by phototryptophan [7], whereas photo β-phenylalanine [8] could replace the β-tyrosine moiety. For photoaffinity labelling studies with seragamides and geodiamolides, D-photophenylalanine could be incorporated.…”