The Structure Elucidation and Total Synthesis of β-Lipomycin

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 28; pp. 7335 - 7338
• Main Authors: Hartmann, Olaf, Kalesse, Markus
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 07.07.2014; WILEY‐VCH Verlag; Wiley
• Subjects: Biological Products - chemical synthesis; Biological Products - chemistry; Chemistry; Chemistry, Multidisciplinary; lipomycins; Molecular Structure; pentaenes; Physical Sciences; Polyketides - chemical synthesis; Polyketides - chemistry; profile hidden Markov model; Pyrrolidinones - chemical synthesis; Pyrrolidinones - chemistry; Science & Technology; structure elucidation; vinylogous Mukaiyama aldol reaction; profile hidden Markov model; ANTIBIOTICS; vinylogous Mukaiyama aldol reaction; CONFIGURATION; FULIGORUBIN-A; STEREOCHEMICAL DETERMINATION; MYXOBACTERIUM-SORANGIUM-CELLULOSUM; TERT-BUTYL 4-DIETHYLPHOSPHONO-3-OXOBUTANETHIOATE; EXHIBITING ANTIBACTERIAL ACTIVITY; lipomycins; pentaenes; MODULAR POLYKETIDE SYNTHASES; structure elucidation; RNA-POLYMERASE INHIBITOR; STEREOSPECIFICITY
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201402259

Here we describe the synthesis of β‐lipomycin, a secondary metabolite isolated from the fermentation broth of Corallococcus coralloides. The synthesis relies on the structural assignment made by a statistical method, the so‐called profile hidden Markov model. Using this protocol, not only the configuration of the secondary alcohol, but also of the adjacent methyl branch could be deduced. The synthesis therefore not only provides access to this natural product but also confirms the validity of this approach for configurational assignment at methyl branches of modular polyketides. Peekaboo with stereocenters: The hidden configuration of natural products can be uncovered using a statistical model to deduce unknown configurations from amino acid sequences of ketoreductases. The synthesis of β‐lipomycin finally confirms the validity of this method in particular for chiral centers in α‐position.