82079-32-1Relevant academic research and scientific papers
Variable synthesis of the optically active thiotetronic acid antibiotics thiolactomycin, thiotetromycin, and 834-B1
Dormann, Korinna L.,Brueckner, Reinhard
, p. 1160 - 1163 (2007)
(Chemical Equation Presented) In seven steps: The antibiotic (+)-thiolactomycin was synthesized in seven steps and with 16% overall yield from 4-acetoxy-2-methyl-2-buten-1-al, an intermediate of the industrial synthesis of vitamin A. Key transformations were the catalytic asymmetric Sharpless epoxidation of an ethoxycarbonyl-substituted pentadienol (93% ee) and a regio- and stereoselective thiolysis of the resulting epoxide (see scheme).
Thiolactomycin-Based Inhibitors of Bacterial β-Ketoacyl-ACP Synthases with in Vivo Activity
Bommineni, Gopal R.,Kapilashrami, Kanishk,Cummings, Jason E.,Lu, Yang,Knudson, Susan E.,Gu, Chendi,Walker, Stephen G.,Slayden, Richard A.,Tonge, Peter J.
, p. 5377 - 5390 (2016)
β-Ketoacyl-ACP synthases (KAS) are key enzymes involved in the type II bacterial fatty acid biosynthesis (FASII) pathway and are putative targets for antibacterial discovery. Several natural product KAS inhibitors have previously been reported, including thiolactomycin (TLM), which is produced by Nocardia spp. Here we describe the synthesis and characterization of optically pure 5R-thiolactomycin (TLM) analogues that show improved whole cell activity against bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and priority pathogens such as Francisella tularensis and Burkholderia pseudomallei. In addition, we identify TLM analogues with in vivo efficacy against MRSA and Klebsiella pneumoniae in animal models of infection.
Lipase-catalyzed kinetic resolution of thiotetronic acid derivatives bearing a chiral quaternary carbon: total synthesis of (R)-thiolactomycin and its O-analogue
Toyama, Ken-ichi,Tauchi, Tetsuo,Mase, Nobuyuki,Yoda, Hidemi,Takabe, Kunihiko
, p. 7163 - 7166 (2006)
We have developed a chemoenzymatic synthesis of (R)-thiolactomycin (1) having a chiral quaternary carbon atom at C5. In the kinetic resolution of the thiotetronic acid precursor 4, both enantiomers were obtained with high enantiomeric excess by use of Chirazyme L-2. Chemical transformations of the (R)-alcohol 4 provided the chiral (R)-thiolactomycin (1) in 36% yield in five steps.
Efficient synthesis and biological activity of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative
Ohata, Kohei,Terashima, Shiro
experimental part, p. 2244 - 2253 (2009/08/07)
The title total synthesis was achieved by employing deconjugative asymmetric α-sulfenylation of the chiral 3-(α,β,γ,δ-unsaturated acyl)oxazolidin-2-one with a 3,3-dimethoxypropyl methanethiosulfonate as a key step. From the biological activity assay carried out using the title compounds, it appeared evident that in vitro antibacterial and mammalian type I FAS inhibitory activity can be cleanly separated by changing not only the substituent at the C3-position but also the absolute configuration at the C5-position, and that unnatural (S)-(-)-3-demethylthiolactomycin and its congeners might be usable as selective mammalian type I FAS inhibitors.
Efficient synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative
Ohata, Kohei,Terashima, Shiro
, p. 2787 - 2791 (2007/10/03)
Starting with commercially available tiglic aldehyde, the title synthesis was achieved by employing deconjugative asymmetric α-sulfenylation of the chiral 3-(α,β,γ,δ-unsaturated acyl)-2-oxazolidinone with a methanethiosulfonate as a key step.
NOVEL COMPUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME
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Page 24, (2010/02/06)
A pharmaceutical composition comprising a phamaceurtical diluent and a compound of formula IV wherein R21= H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, -CH2OR25, -C(O)R25, -CO(O)R25, -C(O)NR25R26, -CH2C(O)R25, or -CH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22 = -OH, -OR27, -OCH2C(O)R27, -OCH2C(O)NHR27, -OC(O)R27, -OC(O)OR27, -OC(O)NHNH-R5, or -OC(O)NR27R28, where R27 and R28 are each independentlyH, C1 -C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R27 and R28 can each optionally contain halogen atoms; R23 and R24, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.
A flexible route to (5R)-thiolactomycin, a naturally occurring inhibitor of fatty acid synthesis.
McFadden, Jill M,Frehywot, Gojeb L,Townsend, Craig A
, p. 3859 - 3862 (2007/10/03)
[formula: see text] A new and efficient asymmetric synthesis of naturally occurring (5R)-thiolactomycin (1) using D-alanine as the source of chirality is described.
