Amythiamicin D
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-00463 |
| CAS | 156620-46-1 |
| Molecular Weight | 1031.26 |
| Molecular Formula | C43H42N12O7S6 |
Online Inquiry
Description
It is produced by the strain of Amycolatopsis sp. M481-42F4. It has activity against gram-positive bacteria including Multidrug resistant Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MR-SA)(MIC 0.1-0.78μg/mL). Not resistant to gram-negative bacteria and fungi.
Specification
| Synonyms | 4-Thiazolecarboxylic acid,2-(10,11,17,18,23,24,25,26,27,28-decahydro-14-methyl-11-(2-(methylamino)-2-oxoethyl)-18,28-bis(1-methylethyl)-9,16,23,26-tetraoxo-9H,16H-8,5:15,12:22,19:32,29:36,33-pentanitrilo-5H,29H,33H-pyrido(3,2-a1)(1,11,18,25,31,4,7,14,21)pentathiatetraazacyclotetratriacontin-2-yl)-,methyl ester |
| IUPAC Name | methyl 2-[21-methyl-18-[2-(methylamino)-2-oxoethyl]-16,23,30,33-tetraoxo-25,35-di(propan-2-yl)-3,13,20,27,37-pentathia-7,17,24,31,34,39,40,41,42,43-decazaheptacyclo[34.2.1.12,5.112,15.119,22.126,29.06,11]tritetraconta-1(38),2(43),4,6(11),7,9,12(42),14,19(41),21,26(40),28,36(39)-tridecaen-8-yl]-1,3-thiazole-4-carboxylate |
| Canonical SMILES | CC1=C2C(=O)NC(C3=NC(=CS3)C(=O)NCC(=O)NC(C4=NC(=CS4)C5=NC(=CS5)C6=C(C=CC(=N6)C7=NC(=CS7)C(=O)OC)C8=NC(=CS8)C(=O)NC(C(=N2)S1)CC(=O)NC)C(C)C)C(C)C |
| InChI | InChI=1S/C43H42N12O7S6/c1-17(2)30-41-51-26(15-67-41)39-48-23(12-64-39)33-20(8-9-21(46-33)38-52-27(16-65-38)43(61)62-7)37-49-25(14-63-37)35(59)47-22(10-28(56)44-6)40-55-32(19(5)68-40)36(60)54-31(18(3)4)42-50-24(13-66-42)34(58)45-11-29(57)53-30/h8-9,12-18,22,30-31H,10-11H2,1-7H3,(H,44,56)(H,45,58)(H,47,59)(H,53,57)(H,54,60) |
| InChI Key | CEKXFMGPQFBJOI-UHFFFAOYSA-N |
Properties
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Density | 1.378 g/cm3 |
| Solubility | Soluble in Methanol |
Reference Reading
1. Solution structures of thiopeptide antibiotics
Richard J Lewis, Rachael A Hughes, Lilian Alcaraz, Stewart P Thompson, Christopher J Moody Chem Commun (Camb). 2006 Oct 28;(40):4215-7. doi: 10.1039/b609282a. Epub 2006 Aug 24.
A detailed NMR study of the thiopeptide amythiamicin D establishes its solution conformation and the presence of a single intramolecular hydrogen bond involving NH13 and O28, and also provides the first evidence for self-association of thiopeptides in solution.
2. Total syntheses of the thiopeptides amythiamicin C and D
Carolin Ammer, Thorsten Bach Chemistry. 2010 Dec 17;16(47):14083-93. doi: 10.1002/chem.201002144.
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.
3. Amythiamicin D and related thiopeptides as inhibitors of the bacterial elongation factor EF-Tu: modification of the amino acid at carbon atom C2 of ring C dramatically influences activity
Stefan Gross, Fabian Nguyen, Matthias Bierschenk, Daniel Sohmen, Thomas Menzel, Iris Antes, Daniel N Wilson, Thorsten Bach ChemMedChem. 2013 Dec;8(12):1954-62. doi: 10.1002/cmdc.201300323. Epub 2013 Sep 17.
Three analogues of amythiamicin D, which differ in the substitution pattern at the methine group adjacent to C2 of the thiazole ring C, were prepared by de novo total synthesis. In amythiamicin D, this carbon atom is (S)-isopropyl substituted. Two of the new analogues carry a hydroxymethyl in place of the isopropyl group, one at an S- (compound 3 a) and the other at an R-configured stereogenic center (3 b). The third analogue, 3 c, contains a benzyloxymethyl group at an S-configured stereogenic center. Compounds 3 b and 3 c showed no inhibitory effect toward various bacterial strains, nor did they influence the translation of firefly luciferase. In stark contrast, compound 3 a inhibited the growth of Gram-positive bacteria Staphylococcus aureus (strains NCTC and Mu50) and Listeria monocytogenes EGD. In the firefly luciferase assay it proved more potent than amythiamicin D, and rescue experiments provided evidence that translation inhibition is due to binding to the bacterial elongation factor Tu (EF-Tu). The results were rationalized by structural investigations and by molecular dynamics simulations of the free compounds in solution and bound to the EF-Tu binding site. The low affinity of compound 3 b was attributed to the absence of a critical hydrogen bond, which stabilizes the conformation required for binding to EF-Tu. Compound 3 c was shown not to comply with the binding properties of the binding site.
Recommended Products
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
| BBF-03754 | CASTANOSPERMINE | Inquiry |
| BBF-03755 | Actinomycin D | Inquiry |
| BBF-01825 | Loganin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
