Floris L. van Delft

Total synthesis of everninomicin 13,384-1--Part 1: retrosynthetic analysis and synthesis of the A1B(A)C fragment.

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-beta-phenylseleno glycosyl fluoride moiety.

Stereocontrolled Synthesis of the Everninomicin A1B(A)C Ring Framework

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(A)C ring fragment 4 of everninomicin 13,384-1.

Expeditious Routes to Evernitrose and Vancosamine Derivatives and Synthesis of a Model Vancomycin Aryl Glycoside

Only seven steps are required to synthesize the activated derivatives 2 and 3 of evernitrose and vancosamine from the common intermediate 1 derived from L-lactic acid. The expeditious route to 3 was followed by its efficient incorporation into a vancomycin model system (4).

Stereoselektive Synthese des Everninomicin-A1B(A)C-Gerüsts

Eine Ringschlusmetathese ist der Schlusselschritt bei der Synthese von 1 aus Divinylmethanol. Aus der gemeinsamen Ausgangsverbindung 1 wurden die aktivierten Derivate 2 und 3 hergestellt, die wiederum als Vorstufen fur die Zuckereinheiten der C- und B-Ringe des synthetisierten A1B(A)C-Gerusts 4 von Everninomicin 13,384-1 dienten.

Einfache Zugänge zu Evernitrose und Vancosaminderivaten sowie Synthese eines Vancomycin-Modellglycosids

In nur sieben Schritten konnen die aktivierten Evernitrose- und Vancosamin-Derivate 2 bzw. 3 aus der gemeinsamen, aus L-Milchsaureethylester zuganglichen Vorstufe 1 hergestellt werden. Die Verbindung 3 ermoglicht eine effizienten Synthese der Vancomycin-Modellverbindung 4.

ortho-Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and Selective Biofunctionalization

Abstract Fast, selective and facile functionalization of biologically relevant molecules is a pursuit of ever‐growing importance. A promising approach in this regard employs the high reactivity of quinone and quinone analogues for fast conjugation chemistry by nucleophilic addition or cycloadditions. Combined with in situ generation of these compounds, selective conjugation on proteins and surfaces can be uniquely induced in a time and spatially resolved manner: generation of a quinone can often be achieved by simple addition of an enzyme or stoichiometric amounts of chemoselective oxidant, or by exposure to light. In this Minireview, we discuss the generation and subsequent functionalization of quinones, iminoquinones, and quinone methides. We also discuss practical applications regarding these conjugation strategies.