Chemoenzymatic Asymmetric Total Synthesis of (R)‐Lasiodiplodin Methyl Ether through a Sulfatase‐Based Deracemization Process. Issue 2 (27th November 2012)

• Record Type: Journal Article
• Authors: Fuchs, Michael; Toesch, Michael; Schober, Markus; Wuensch, Christiane; Faber, Kurt
• Is Part Of: European journal of organic chemistry. Issue 2(2013)
• Page Start: 356
• Page End: 361
• Publication Date: 2012-11-27
• Subjects: Medicinal chemistry -- Natural products -- Total synthesis -- Enantioselecti­vity -- Chiral resolution -- Asymmetric catalysis­ -- Cleavage reactions; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201201296
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: ( R )‐Lasiodiplodin methyl ether, a precursor of the antileukemic agent lasiodiplodin, was synthesized through a seven‐step linear sequence. Chirality was introduced through a sulfatase‐based deracemization process, in which a functionalized ( rac )‐ sec ‐sulfate ester was enzymatically hydrolyzed with inversion of the stereocenter using an alkyl sulfatase. The remaining sulfate ester enantiomer was hydrolyzed with retention of configuration under acidic conditions, yielding the chiral key building block as the sole product in 93 % ee The total synthesis was completed through Negishi cross‐coupling and ring‐closing metathesis. Abstract : Lasiodiplodin methyl ether, a precursor of the antileukemic agent lasiodiplodin, was synthesized through a seven‐step chemoenzymatic route. The central chiral building block was obtained through a sulfatase‐based deracemization protocol, which furnished a single stereoisomer in 93 % ee from the racemate.