FR901459
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| Category | Antibiotics |
| Catalog number | BBF-03570 |
| CAS | 155144-72-2 |
| Molecular Weight | 1218.61 |
| Molecular Formula | C62H111N11O13 |
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Description
FR901459, a product of the fungus Stachybotrys chartarum No. 19392, is a derivative of cyclosporin A (CsA) and a powerful immunosuppressant that binds cyclophilin. Its immunosuppressive effect was lower than that of cyclostatin A.
Specification
| IUPAC Name | (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-[(1R)-1-hydroxyethyl]-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,10,12,15,19,25,28-octamethyl-6,9,18,21,24-pentakis(2-methylpropyl)-3-propan-2-yl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone |
| Canonical SMILES | CC=CCC(C)C(C1C(=O)NC(C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)N1C)C(C)C)C)CC(C)C)CC(C)C)C)C)C)CC(C)C)C)CC(C)C)CC(C)C)C)C)C(C)O)O |
| InChI | InChI=1S/C62H111N11O13/c1-24-25-26-39(14)52(76)51-57(81)67-49(42(17)74)61(85)68(18)32-48(75)69(19)45(29-35(6)7)55(79)65-43(27-33(2)3)59(83)71(21)46(30-36(8)9)54(78)63-40(15)53(77)64-41(16)58(82)70(20)47(31-37(10)11)56(80)66-44(28-34(4)5)60(84)72(22)50(38(12)13)62(86)73(51)23/h24-25,33-47,49-52,74,76H,26-32H2,1-23H3,(H,63,78)(H,64,77)(H,65,79)(H,66,80)(H,67,81)/b25-24+/t39-,40+,41-,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1 |
| InChI Key | RXQFIJPCAOCJDB-FMOTYOMISA-N |
Properties
| Appearance | White Powder |
| Melting Point | 156-158°C |
Reference Reading
1. Strain improvement of Lentzea sp. 7887 for higher yield per unit volume on hydroxylation of cyclosporine derivative FR901459
Tetsuya Yabutani, Mami Tsujimoto, Shunsuke Ohira, Shiho Shimizu, Hideo Nakano Biosci Biotechnol Biochem. 2017 Jul;81(7):1456-1459. doi: 10.1080/09168451.2017.1314759. Epub 2017 Apr 13.
A Gram-positive bacterium Lentzea sp. 7887 hydroxylates a cyclosporine derivative FR901459 into AS1837812 (9-hydroxide), which is an important intermediate of candidate drugs that target the hepatitis C virus. We screened a UV-induced mutant, named M-1, which showed about 1.2-fold higher conversion yields, 2-fold higher substrate concentrations (3.69 mM), and 2.5-fold higher yield per unit volume than the wild-type strain.
2. Discovery of a novel 9-position modified second-generation anti-HCV candidate via bioconversion and semi-synthesis of FR901459
Takuya Makino, Junya Ishida, Toshio Yamanaka, Hidenori Ohki, Masao Uchida, Masae Sawada, David Barrett Bioorg Med Chem Lett. 2020 Sep 15;30(18):127423. doi: 10.1016/j.bmcl.2020.127423. Epub 2020 Jul 21.
Evidence that hepatitis C virus (HCV) utilizes cellular cyclophilin proteins in the virus replication cycle has increased attention on cyclophilin inhibitors as attractive therapeutic targets in the treatment of HCV. Previous reports have described a number of non-immunosuppressive cyclophilin inhibitors, most of which require many synthetic steps for their preparation. Sasamura et al. have previously reported the isolation of bioconversion derivative 4. This analog is a convenient starting point for optimization due to the presence of the readily modifiable primary hydroxyl group and because it shows moderate anti-HCV activity and decreased immunosuppressive activity. We have also established an efficient C-alkylation reaction at the 3-position. Through a detailed structure-activity relationship study, we discovered a new type of clinical candidate 14 which requires a short synthetic process and has potent anti-HCV activity and reduced immunosuppressive activity, as well as improved aqueous solubility and pharmacokinetics.
3. Development of an efficient semisynthetic modification of FR901459 via a novel regioselective N, O-acyl migration
Takuya Makino, Seiji Yoshimura, Toshio Yamanaka, Masae Sawada, David Barrett Bioorg Med Chem Lett. 2020 Jul 15;30(14):127251. doi: 10.1016/j.bmcl.2020.127251. Epub 2020 May 7.
HCV utilizes cellular protein cyclophilins in the virus replication cycle and cyclophilin inhibitors have become a new class of anti-HCV agents. In our screening of natural products, we identified a unique cyclosporin analogue, FR901459, as a cyclophilin inhibitor with potent anti-HCV activity. In this work, we developed an efficient synthetic methodology to prepare FR901459 derivatives via an N, O-acyl migration reaction. This method allows us to efficiently manipulate the amino acid residues at the 3 position while avoiding lengthy total synthesis for each compound. By using this methodology, we discovered 4, which has superior anti-HCV activity and decreased immunosuppressive activity compared to FR901459.
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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 ╳
