Acetic acid (2S,3R,4S,6R)-4-dimethylamino-2-((3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-oxacyclotetradec-6-yloxy)-6-methyl-tetrahydro-pyran-3-yl ester | 143353-82-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Acetic acid (2S,3R,4S,6R)-4-dimethylamino-2-((3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-oxacyclotetradec-6-yloxy)-6-methyl-tetrahydro-pyran-3-yl ester
• 英文别名: [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] acetate
• CAS: 143353-82-6
• 化学式: C₃₂H₅₅NO₁₁
• 分子量: 629.789
• InChiKey: YZCZTRXLLDSVJW-VBFGOBDLSA-N

物化性质

• 沸点：
  709.8±60.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Acetic acid (2S,3R,4S,6R)-4-dimethylamino-2-((3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-oxacyclotetradec-6-yloxy)-6-methyl-tetrahydro-pyran-3-yl ester 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 11-N-(4-azido-butyl)-6-O-methyl-5-(2-acetyl-desosamynyl)-3-oxo-erythronolide A 11,12-carbamate
  参考文献：
  名称：

  Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome

  摘要：

  Despite decades of research on the bacterial ribosome, the ribosomal exit tunnel is still poorly understood. Although it has been suggested that the exit tunnel is simply a convenient route of egress for the nascent chain, specific protein sequences serve to slow the rate of translation, suggesting some degree of interaction between the nascent peptide chain and the exit tunnel. To understand how the ribosome interacts with nascent peptide sequences, we synthesized and characterized a novel class of probe molecules. These peptidemacrolide (or peptolide) conjugates were designed to present unique peptide sequences to the exit tunnel. Biochemical and X-ray structural analyses of the interactions between these probes and the ribosome reveal interesting insights about the exit tunnel. Using translation inhibition and RNA structure probing assays, we find the exit tunnel has a relaxed preference for the directionality (N -> C or C -> N orientation) of the nascent peptides. Moreover, the X-ray crystal structure of one peptolide derived from a positively charged, reverse Nuclear Localization Sequence peptide, bound to the 70S bacterial ribosome, reveals that the macrolide ring of the peptolide binds in the same position as other macrolides. However, the peptide tail folds over the macrolide ring, oriented toward the peptidyl transferase center and interacting in a novel manner with 23S rRNA residue C2442 and His69 of ribosomal protein L4. These data suggest that these peptolides are viable probes for interrogating nascent peptideexit tunnel interaction.

  DOI：

  10.1021/cb5003224
• 作为产物：
  描述：

  2'-O-acetyl-6-O-methylerythromycin A 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成 Acetic acid (2S,3R,4S,6R)-4-dimethylamino-2-((3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-oxacyclotetradec-6-yloxy)-6-methyl-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  A Facile and Scaleable Synthesis of 3-O-Decladinose-6-methyl-10,11-dehydrate-erythromycin-3-one-2‘-acetate, an Important Intermediate for Ketolide Synthesis

  摘要：

  A facile and scaleable synthetic process of compound 2, an important intermediate for synthesis of ketolide semisynthetic antibiotics, was developed starting from commercially available clathromycin with an overall yield of similar to 74%. This synthetic pathway was composed of four steps from compound 3 which could be prepared from clathromycin without using expensive reagents such as EDC, HCl (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) or more active reagents such as methanesulfonic anhydride. This new process was efficient and practical as demonstrated by scale-up to prepare more than 1 kg of pure compound 2.

  DOI：

  10.1021/op060001x

文献信息

• Synthesis of 14,15-Dehydroerythromycin A Ketolides: Effects of the 13-Substituent on Erythromycin Tautomerism.
  作者：MARIA FARDIS、GARY W. ASHLEY、JOHN R. CARNEY、DANIEL T. CHU

  DOI：10.7164/antibiotics.54.278

  日期：——

  A ketolide was prepared from 14, 15-dehydroerythromycin A by two different routes. The first approach involving oxidation of the 3-OH of 3-descladinosyl-14, 15-dehydroerythromycin A 2'-O-acetate gave unexpectedly high levels of 3, 11-double oxidation. This may be due to greater formation of the 9, 12-hemiketal in 14, 15-dehydroerythromycin A and concomitant exposure of the 11-OH group for oxidation. NMR studies of 14, 15-dehydroerythromycin A support this hypothesis, revealing a 9:1 ratio of 9-ketone to 9, 12-hemiketal in CDC13 and a 1: 1 ratio in CD3OD as contrasted with the corresponding tautomer ratios of 30:1 in CDC13, and 6:1 in CD3OD with erythromycin A. Alteration of the 13-substituent on the erymronolide A ring from ethyl to vinyl thus favors formation of the 9, 12-hemiketal. A second route to the ketolides was developed based on these findings, in which the 11-OH is eliminated prior to oxidation of the3-OH.

  通过两种不同的路线从14, 15-脱氢红霉素A制备了酮类化合物。第一种方法涉及对3-脱落氨基-14, 15-脱氢红霉素A 2'-O-醋酸酯的3-OH进行氧化，意外地产生了高水平的3, 11-双氧化。这可能是由于在14, 15-脱氢红霉素A中9, 12-半缩酮的形成增加，同时11-OH基团暴露于氧化反应中。对14, 15-脱氢红霉素A的核磁共振（NMR）研究支持了这一假设，显示在CDC13中的9-酮与9, 12-半缩酮的比例为9:1，而在CD3OD中则为1:1，与红霉素A在CDC13和CD3OD中对应的量子异构体比例30:1和6:1形成对比。将红霉素A环上的13-取代基从乙基更改为乙烯基，从而有利于9, 12-半缩酮的形成。基于这些发现，发展了第二种制备酮类化合物的路线，其中在氧化3-OH之前先消除11-OH。
• Novel process for the preparation of telithromycin
  申请人：Deshpande Pandurang Balwant

  公开号：US20080051352A1

  公开（公告）日：2008-02-28

  The present invention relates to the process for the preparation of compounds of formula (I) or its pharmaceutically acceptable salts wherein, R is

  本发明涉及制备式(I)化合物或其药学上可接受的盐的过程，其中R为
• Erythromycin compounds
  申请人：Roussel Uclaf

  公开号：US05635485A1

  公开（公告）日：1997-06-03

  An erythromycin compound of Formula I or its non-toxic acid addition salt having antibiotic activity.

  具有抗生素活性的式I的红霉素化合物或其非毒性酸加成盐。
• Eryhromycin derivatives
  申请人：Roussel Uclaf

  公开号：US05614614A1

  公开（公告）日：1997-03-25

  Novel intermediates for the preparation of the compounds of Formula I wherein the substituents are as defined in the specification.

  为制备式I化合物中定义的取代基的新型中间体。
• Synthesis and Antibacterial Activity of Ketolides (6-<i>O</i>-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens
  作者：Constantin Agouridas、Alexis Denis、Jean-Michel Auger、Yannick Benedetti、Alain Bonnefoy、François Bretin、Jean-François Chantot、Arlette Dussarat、Claude Fromentin、Solange Gouin D'Ambrières、Sylvette Lachaud、Patrick Laurin、Odile Le Martret、Véronique Loyau、Nicole Tessot

  DOI：10.1021/jm980240d

  日期：1998.10.1

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.