20-dihydrotylosin | 1404-48-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 20-dihydrotylosin
• 英文别名: relomycin；tylosin D；(4R,5S,6S,7R,9R,11E,13E,15R,16R)-6-[(2R,3R,4R,5S,6R)-5-[(2S,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-7-(2-hydroxyethyl)-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
• CAS: 1404-48-4
• 化学式: C₄₆H₇₉NO₁₇
• 分子量: 918.13
• InChiKey: QDAVFUSCCPXZTE-VMXQISHHSA-N

物化性质

• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  64
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  242
• 氢给体数：
  6
• 氢受体数：
  18

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  泰乐菌素	tylosin	1401-69-0	C46H77NO17	916.114

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  泰乐菌素	tylosin	1401-69-0	C46H77NO17	916.114
  ——	20-dihydro-20-deoxy-20-fluorotylosin	91677-92-8	C46H78FNO16	920.121
  ——	20-dihydro-20-deoxy-20-chlorotylosin	91661-57-3	C46H78ClNO16	936.575
  ——	20-dihydro-20-(hexafluoroisopropyl)tylosin	91662-05-4	C49H79F6NO17	1068.15
  ——	20-dihydro-20-deoxy-20-azidotylosin	91661-63-1	C46H78N4O16	943.143
  ——	20-dihydro-20-O-phenyltylosin	91661-59-5	C52H83NO17	994.228
  ——	20-dihydro-20-deoxy-20-phenylthiotylosin	91661-97-1	C52H83NO16S	1010.29
  ——	20-dihydro-20-O-phenyl-2'-O-acetyltylosin	91661-68-6	C54H85NO18	1036.26
  ——	20-dihydro-20-deoxy-20-<(1-methyl-5-tetrazolyl)thio>tylosin	91661-55-1	C48H81N5O16S	1016.26
  泰乐菌素B	tylosin B	11032-98-7	C39H65NO14	771.943

反应信息

• 作为反应物：
  描述：

  20-dihydrotylosin 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 碳酸氢钠 、 potassium bromide 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 生成 泰乐菌素
  参考文献：
  名称：

  一种以泰乐菌素D为原料制备替米考星的方 法

  摘要：

  本发明涉及一种以泰乐菌素D为原料制备替米考星的方法，该方法以泰乐菌素D为原料，通过选择性氧化剂将20位伯羟基氧化为醛基得到中间体1，再水解脱碳霉糖得到中间体2，通过甲酸与3,5二甲基哌啶还原氨化反应得到产品替米考星。本发明以泰乐菌素D为原料，通过特定的选择性氧化剂使泰乐菌素D转变为合成替米考星的有效成分，避免转变为杂质，为替米考星的制备开辟了一条新途径，解决了现有以泰乐菌素为起始原料制备替米考星的杂质残留高与收率偏低的问题。

  公开号：

  CN106905397B
• 作为产物：
  描述：

  泰乐菌素 在 sodium tetrahydroborate 、 pH 7.5 buffer 作用下， 以 甲醇 为溶剂， 生成 20-dihydrotylosin
  参考文献：
  名称：

  由泰乐菌素诱变合成23 - O-胞嘧啶基12,13-脱环氧基-12,13-二氢-玫瑰香素

  摘要：

  rosaramicin和mycinamicin的杂合结构已被突变合成，并且发现对革兰氏阳性生物具有高度活性。

  DOI：

  10.1039/c39820000855

文献信息

• Structure-activity relationship among polyhydro derivatives of tylosin.
  作者：AMALIA NARANDJA、BOZIDAR ŠUŠKOVIC、ZELJKO KELNERIC、SLOBODAN DJOKIC

  DOI：10.7164/antibiotics.47.581

  日期：——

  Tetra-, hexa-and octahydro derivatives of tylosin were prepared by the reduction of the conjugated double bond and carbonyl groups. Hydrogenation of the diene did not change the in vitro antimicrobial activity of compounds, while reduction of carbonyls causes small or complete loss of activity.

  通过还原共轭双键和羰基，制备了泰乐菌素的四氢、六氢和八氢衍生物。二烯的氢化不会改变化合物的体外抗菌活性，而羰基的还原则会导致活性的少量或完全丧失。
• Sorption of tylosin A, D, and A‐aldol and degradation of tylosin a in soils
  作者：Stephen A. Sassman、Ajtt K. Sarmah、Linda S. Lee

  DOI：10.1897/07-007r.1

  日期：2007.8

  Heightened concerns regarding the potential impact on soil and water quality of veterinary antibiotics warrant a better understanding of the environmental fate of antibiotics in soil. Sorption of the macrolides tylosin A (TA), tylosin D, and TA‐aldol was measured in several soils and evaluated with respect to soil pH, organic matter content, percentage clay, and cation‐exchange capacity (CEC). Tylosin and related compounds exhibit similar sorption characteristics and generally are strongly sorbed, with sorption being well and positively correlated to surface area, clay content, and CEC. Sorption coefficients normalized by CEC were within a narrow range (10^4.1±0.21 L/mol_c) for all but one soil; however, good extraction recoveries with only methanol for most soils suggested that hydrophobic processes also contribute to sorption. Aerobic degradation of TA over a three‐month period in two freshly collected agricultural soils and ⁶⁰Co‐irradiated soils indicated that both abiotic and microbial processes contribute to TA transformation. The abiotic process was much slower and dominated in the first two weeks, followed by rapid microbial degradation within 3 d. Three primary degradation products were identified using liquid chromatography with full‐scan mass spectrometry, with unconfirmed identifications of TA having the aldehyde group oxidized to an acid (m/z = 932) in both soils and tyslosin B (m/z = 772) as well as tylosin B having the aldehyde group oxidized to an acid (m/z = 788) in the sandy soil.

  摘要人们日益关注兽用抗生素对土壤和水质的潜在影响，因此需要更好地了解抗生素在土壤中的环境归宿。在几种土壤中测量了大环内酯类药物泰乐菌素 A (TA)、泰乐菌素 D 和 TA-aldol 的吸附性，并根据土壤 pH 值、有机物含量、粘土百分比和阳离子交换容量 (CEC) 进行了评估。泰乐菌素和相关化合物表现出相似的吸附特性，通常具有很强的吸附性，吸附性与表面积、粘土含量和阳离子交换容量呈良好的正相关。除一种土壤外，所有土壤的吸附系数（以 CEC 归一化）都在很小的范围内（104.1±0.21 L/molc）；然而，大多数土壤仅用甲醇就能获得很好的萃取回收率，这表明疏水过程也有助于吸附。在两个新采集的农业土壤和 60Co-irradiated 土壤中，TA 在三个月内的有氧降解表明，非生物过程和微生物过程都有助于 TA 的转化。非生物过程要慢得多，在头两周内占主导地位，随后在 3 d 内迅速发生微生物降解。使用液相色谱法和全扫描质谱法确定了三种主要降解产物，在两种土壤中，醛基被氧化成酸（m/z = 932）的 TA 和沙质土壤中的泰乐菌素 B（m/z = 772）以及醛基被氧化成酸（m/z = 788）的泰乐菌素 B 均未被证实。
• Synthesis and evaluation of tylosin-related macrolides modified at the aldehyde function: a new series of orally effective antibiotics
  作者：Herbert A. Kirst、John E. Toth、Manuel Debono、Kevin E. Willard、Brenda A. Truedell、John L. Ott、Fred T. Counter、Anna M. Felty-Duckworth、Robert S. Pekarek

  DOI：10.1021/jm00403a025

  日期：1988.8

  Modification of the aldehyde group in tylosin and related macrolide antibiotics dramatically enhanced the oral efficacy of the derivatives against experimental infections caused by susceptible bacteria in laboratory animals. A large number and wide variety of aldehyde-modified macrolide derivatives were prepared, utilizing the Mitsunobu reaction and other chemical transformations. Evaluation of in vitro and in vivo antimicrobial activity indicated that derivatives of demycarosyltylosin (desmycosin) combined the broadest spectrum of antimicrobial activity with the best efficacy and bioavailability after oral administration.
• Interplay between the Ribosomal Tunnel, Nascent Chain, and Macrolides Influences Drug Inhibition
  作者：Agata L. Starosta、Viktoriya V. Karpenko、Anna V. Shishkina、Aleksandra Mikolajka、Natalia V. Sumbatyan、Frank Schluenzen、Galina A. Korshunova、Alexey A. Bogdanov、Daniel N. Wilson

  DOI：10.1016/j.chembiol.2010.04.008

  日期：2010.5

  Accumulating evidence suggests that, during translation, nascent chains can form specific interactions with ribosomal exit tunnel to regulate translation and promote initial folding events. The clinically important macrolide antibiotics bind within the exit tunnel and inhibit translation by preventing progression of the nascent chain and inducing peptidyl-tRNA drop-off. Here, we have synthesized amino acid- and peptide-containing macrolides, which are used to demonstrate that distinct amino acids and peptides can establish interaction with components of the ribosomal tunnel and enhance the ribosome-binding and inhibitory properties of the macrolide drugs, consistent with the concept that the exit tunnel is not simply a Teflon-like channel. Surprisingly, we find that macrolide antibiotics do not inhibit translation of all nascent chains similarly, but rather exhibit polypeptide-specific inhibitory effects, providing a change to our general mechanistic understanding of macrolide inhibition.
• KIRST, HERBERT A.;TOTH, JOHN E.;DEBONO, MANUEL;WILLARD, KEVIN E.;TRUEDELL+, J. MED. CHEM., 31,(1988) N 8, C. 1631-1641
  作者：KIRST, HERBERT A.、TOTH, JOHN E.、DEBONO, MANUEL、WILLARD, KEVIN E.、TRUEDELL+

  DOI：——

  日期：——