- Novel antibiotics, amythiamicins - III. Structure elucidations of amythiamicins A, B and C
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The structures of novel antimicrobial antibiotics, amythiamicins A, B and C, were elucidated by chemical degradations and NMR spectral analyses. The main frame from C-1 to C-41 of these antibiotics was the same as that of amythiamicin D. Amino acid autoanalyses of amythiamicins A, B and C showed that these have another one mole of serine and proline in comparison with amythiamicin D. Stereochemistries of both amino acids were determined to be L by chiral HPLC. These seryl-prolyl residues in amythiamicins A, B and C are attached at C-41 through an oxazoline ring, amide and ester bond, respectively.
- Shimanaka,Takahashi,Inuma,Naganawa,Takeuchi
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- Total syntheses of the thiopeptides smythiamicin C and D
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The thiopeptides amythiamicin C and D were synthesized by employing amide bond formation, a Stille cross-coupling reaction, and two Negishi cross-coupling reactions as key transformations. The central 2,3,6-trisubstituted pyridine ring of the target compounds was introduced as a 2,6-dibromo-3-iodopyridine, which was selectively metalated at the 3-position and connected to the complete Southern fragment of the amythiamicins by a Negishi cross-coupling. For the synthesis of amythiamicin C, this step was followed by a Negishi cross-coupling at C-6 of the pyridine core. Subsequent attachment of the Eastern fragment was achieved by amide bond formation and macrolactam ring closure by a Stille cross-coupling at C-2. The Eastern bithiazole fragment of the amythiamins was constructed also by regioselective metalation and cross-coupling reactions. The pivotal step involved the diastereoselective addition of 4-bromothiazole-2- magnesium bromide to a chiral sulfinyl imine. For the synthesis of amythiamicin D, the order of cross-coupling at C-6, amide bond formation, and cross-coupling at C-2 was changed. The amide bond formation to the Eastern fragment was performed first and it was subsequently attempted to close the macrolactam by an intramolecular regioselective Stille cross-coupling at C-2. Despite the low regioselectivity of this reaction it paved the way to the immediate completion of the amythiamicin D synthesis when followed by a Negishi cross-coupling at C-6 with 2-zincated methyl thiazole-5-carboxylate. Cross-coupling reactions paved the way to two short syntheses of amythiamicin C (1) and D (2; see scheme). In the former synthesis, the sequence A-C-B was followed to give access to the title compound 1. In the latter synthesis, the sequence C-B-A was probed and led successfully to amythiamicin D (2) in an extremely short, but less selective, synthetic sequence.
- Ammer, Carolin,Bach, Thorsten
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p. 14083 - 14093
(2011/02/22)
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- Total synthesis of the thiopeptide antibiotic amythiamicin D
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The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thi
- Hughes, Rachael A.,Thompson, Stewart P.,Alcaraz, Lilian,Moody, Christopher J.
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p. 15644 - 15651
(2007/10/03)
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- Total synthesis of the thiopeptide amythiamicin D.
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The first total synthesis of the thiopeptide antibiotic amythiamicin D is described.
- Hughes, Rachael A,Thompson, Stewart P,Alcaraz, Lilian,Moody, Christopher J
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p. 946 - 948
(2007/10/03)
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