- Total synthesis of thiangazole
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A method for total synthesis of thiangazole (1), a tris-thiazoline- oxazole metabolite, is described. The key intermediate 9, a linear tetrapeptide amide composed of three S-benzyl-2-methylcysteine residues and a O-benzyl-threonine amide, was synthesized in 4 steps using 2-chloro-1,3- dimethyl-imidazolidium hexafluorophosphate(CIP)mediated activation. The successive thiazoline/oxazole rings were constructed by TiCl4mediated cycledehydration followed by acid-catalyzed Robinson-Gabriel reaction without difficulty.
- Akaji, Kenichi,Kiso, Yoshiaki
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p. 10685 - 10694
(2007/10/03)
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- Chemical modification of thiangazole A in the oxazole and styryl region
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The partial synthesis of 54 derivatives of thiangazole A (1a), a new polythiazoline antibiotic from Polyangium spec. (myxobacteria), is described. Derivatives with chemical modification of the carboxamide group in the oxazole region were prepared either by N-alkylation to amides 5-14 or by methanolysis to ester 15, and its transformation products 16, 19, 20. Oxidation of the C-5 methyl group of 1a with molecular oxygen led to the hydroxymethyl derivative 21, and two by-products lacking the C-5 methyl group (22), or the entire oxazole ring (23). Key intermediate for analogues with modifications in the styryl region is the aldehyde 27, obtained by direct cleavage of the C-21/C-22 double bond. 27 was transformed into the oximes 37- 42 and by Wittig reaction to (21Z)-thiangazole (43) and analogues 44-46 with proton and alkyl residues replacing phenyl. 21,22-Didehydrothiangazo1e (50) was synthesized in a multi-step reaction from 27 via the 20-alkinyl intermediate 49. The insecticidal activities and inhibition of the respiratory chain (complex I) by the thiangazole analogues were determined and compared with the natural product.
- Herrmann, Martina,Ehrler, Juerg,Kayser, Hartmut,Rindlisbacher, Alfred,Hoefle, Gerhard
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p. 3381 - 3392
(2007/10/03)
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- From Aziridines to Oxazolines and Thiazolines: The Heterocyclic Route to Thiangazole
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Since its isolation in 1991, the polyazole natural product thiangazole has become a popular target for total synthesis due to its challenging array of heterocyclic segments and its reported potent antiviral activity. The synthetic activity toward thiangazole is reviewed and a novel approach that takes advantage of aziridine and oxazoline intermediates en route to thiazolines is presented.
- Wipf, Peter,Venkatraman, Srikanth
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- Natural Products as Pesticides: Two Examples of Stereoselective Synthesis
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The strategy and synthetic efforts leading to efficient stereoselective syntheses of thiangazole, a tris-thiazolinyl-oxazole metabolite isolated from Polyangium spp., and hydantocidin, a spironucleoside metabolite isolated from Streptomyces hygroscopicus, are discussed.
- Frueh, Thomas,Chemla, Philippe,Ehrler, Juerg,Farooq, Saleem
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- Total synthesis of thiangazole, a novel naturally occurring HIV-1 inhibitor from Polyangium sp
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The total synthesis of the cinnamyl-oxazole substituted tris-thiazoline containing metabolite (-)-thiangazole (1) is described. The synthesis is based on elaboration of the R-2-methylcysteine derived bis-thiazoline nitrile (5) and oxazole (6) intermediate
- Boyce, Richard J.,Mulqueen, Gerard C.,Pattenden, Gerald
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p. 7321 - 7330
(2007/10/02)
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- Total Synthesis of (-)-Thiangazole and Structurally Related Polyazoles
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Thiangazole was reported to be an extremely potent, nontoxic inhibitor of HIV-1 in MT4 cell assays.By employing a strategy of selective oxazoline-thiazoline interconversions, we have accomplished a total synthesis of the natural product in 16 steps and 1.1percent overall yield from (S)-α-methylserine.This new methodology is especially useful for the preparation of analogs of thiangazole and structure-activity studies.Our preliminary biological testing of (-)-thiangazole revealed a high level of cytotoxicity that was considerably reduced in the oxazoline-containing analogs.
- Wipf, Peter,Venkatraman, Srikanth
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p. 7224 - 7229
(2007/10/03)
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- Total synthesis of thiangazole, a novel inhibitor of HIV-1 from Polyangium sp
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A concise total synthesis of the cinnamyl-oxazole substituted tris- thiazoline containing metabolite thiangazole 1 is described.
- Boyce, Richard J.,Mulqueen, Gerard C.,Pattenden, Gerald
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p. 5705 - 5708
(2007/10/02)
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