214483-50-8Relevant academic research and scientific papers
Total synthesis of everninomicin 13,384-1 - Part 1: Retrosynthetic analysis and synthesis of the A1B(A)C fragment
Nicolaou,Rodriguez, Rosa Maria,Mitchell, Helen J.,Suzuki, Hideo,Fylaktakidou, Konstantina C.,Baudoin, Olivier,Van Delft, Floris L.
, p. 3095 - 3115 (2007/10/03)
In this first of a series of four articles we introduce everninomicin 13,384-1 (1), a powerful antibiotic effective against drug resistant bacteria, as a target for total synthesis and discuss its retrosynthetic analysis. From the three defined fragments required for the synthesis (2: A1B(A)C fragment; 4: DE fragment; 5: FGHA2 fragment), we describe herein two approaches to the A1B(A)C block. The first strategy relied on an olefin metathesis reaction to construct a common intermediate for rings B and C, but was faced with final protecting group problems. The second, and successful approach, involved a 1,2-phenylsulfeno migration and a sulfur directed glycosidation procedure to link rings B and C, as well as an acyl fluoride intermediate to install the sterically hindered aryl ester moiety (ring A1). The final stages of the synthesis of the required 2-phenylseleno glycosyl fluoride 2 required introduction of a phenylseleno group at C-1 of ring C followed by a novel, DAST-promoted 1,2-migration to produce the desired 2-β-phenylseleno glycosyl fluoride moiety.
Total synthesis of everninomicin 13,384-1 - Part 1: Synthesis of the A1B(A)C fragment
Nicolaou,Mitchell, Helen J.,Suzuki, Hideo,Rodriguez, Rosa Maria,Baudoin, Olivier,Fylaktakidou, Konstantina C.
, p. 3334 - 3339 (2007/10/03)
The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The (1 → 1-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.
Stereocontrolled synthesis of the everninomicin A1B(A)C ring framework
Nicolaou,Rodriguez, Rosa M.,Mitchell, Helen J.,Van Delft, Floris L.
, p. 1874 - 1876 (2007/10/03)
A strategy based on a ring-closing olefin metathesis was used to convert divinylmethanol into 1, which served as a common precursor to activated derivatives 2 and 3. These in turn serve as precursors to the C and B carbohydrate units of the A1B
