10148-69-3Relevant academic research and scientific papers
Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores
Zwick, Christian R.,Sosa, Max B.,Renata, Hans
supporting information, p. 1673 - 1679 (2021/01/25)
The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.
Synthesis of γ-halogenated and long-chain β-hydroxy-α-amino acids and 2-amino-1,3-diols using threonine aldolases
Steinreiber, Johannes,Fesko, Kateryna,Mayer, Clemens,Reisinger, Christoph,Schürmann, Martin,Griengl, Herfried
, p. 8088 - 8093 (2008/02/08)
The l- and d-threonine aldolase catalyzed formation of γ-halogenated and long-chain l- and d-3-alkylserine-derivatives 1-12, respectively, was shown starting from glycine and halogenated C2- or C4-C12 aldehydes. lTA from Pseudomonas putida accepted all tested aldehydes with strongly varying diastereoselectivity (de up to 93%). Only aldehydes smaller than decanal were converted by dTA from Alcaligenes xylosoxidans with good selectivities (de up to 73%). Utilizing isobutanal enantio- and diastereopure d-syn-2-amino-3-hydroxy-4-methylpentanoic acid was obtained (ee>99%, de>95%), which was converted to the corresponding 2-amino-1,3-diol.
Application of enantiopure templated azomethine ylids to β-hydroxy-α- amino acid synthesis
Alker, David,Hamblett, Giles,Harwood, Laurence M.,Robertson, Sarah M.,Watkin, David J.,Williams, C. Eleri
, p. 6089 - 6098 (2007/10/03)
Chiral stabilised azomethine ylids derived from the reaction of (5S)-5- phenylmorpholin-2-one (1) with aldehydes undergo efficient and highly diastereocontrolled cycloaddition with a second molecule of aldehyde to furnish products (2) which may be converted into enantiomerically pure threo (2S,3R) β-hydroxy-α-amino acids (3) in excellent yield.
ASYMMETRIC ALDOL REACTIONS USING BORON ENOLATES OF CHIRAL OXAZINONES, SYNTHESIS OF L-ALLO-THREONINE
Reno, Daniel S.,Lotz, Bruce T.,Miller, Marvin J.
, p. 827 - 830 (2007/10/02)
The boron enolate of oxazinone 1 was allowed to react with acetaldehyde, butanal, and 2-methylpropanal.The reaction proceeded stereoselectively, and in the reaction with acetaldehyde, the reaction afforded a precursor to L-allo-threonine.
