title: Biocatalytic Synthesis of Allylic and Allenyl Sulfides through a Myoglobin-Catalyzed Doyle-Kirmse Reaction.
abstract: The first example of a biocatalytic [2,3]-sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle-Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C-C bond-forming transformation with high efficiency and product conversions across a variety of sulfide substrates (e.g., aryl-, benzyl-, and alkyl-substituted allylic sulfides) and α-diazo esters. Moreover, the scope of this myoglobin-mediated transformation could be extended to the conversion of propargylic sulfides to give substituted allenes. Active-site mutations proved effective in enhancing the catalytic efficiency of the hemoprotein in these reactions as well as modulating the enantioselectivity, resulting in the identification of the myoglobin variant Mb(L29S,H64V,V68F), which is capable of mediating asymmetric Doyle-Kirmse reactions with an enantiomeric excess up to 71 %. This work extends the toolbox of currently available biocatalytic strategies for the asymmetric formation of carbon-carbon bonds.
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627, USA.
authors.forename: Vikas
authors.identifier: 0000-0002-8946-5773
authors.initials: V
authors.lastname: Tyagi
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627, USA.
authors.forename: Gopeekrishnan
authors.initials: G
authors.lastname: Sreenilayam
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627, USA.
authors.forename: Priyanka
authors.identifier: 0000-0002-2235-8746
authors.initials: P
authors.lastname: Bajaj
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627, USA.
authors.forename: Antonio
authors.identifier: 0000-0003-3960-9457
authors.initials: A
authors.lastname: Tinoco
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627, USA. rfasan@ur.rochester.edu.
authors.forename: Rudi
authors.identifier: 0000-0003-4636-9578
authors.initials: R
authors.lastname: Fasan
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry / Q000378:metabolism*; D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D015394:Molecular Structure; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism*; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000498:Allyl Compounds; D001391:Azo Compounds; D009211:Myoglobin; D013440:Sulfides; C038491:allyl sulfide
keywords: biocatalysis; heme proteins; protein engineering; sigmatropic rearrangement; ylides