(S)-2-hydroxy-3-methylbutyric acid benzhydryl ester | 70362-55-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-2-hydroxy-3-methylbutyric acid benzhydryl ester
• 英文别名: benzhydryl (2S)-2-hydroxy-3-methylbutanoate
• CAS: 70362-55-9
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: UREJCUOEOIUSMT-INIZCTEOSA-N

物化性质

• 熔点：
  77.5-78.8 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  402.0±30.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-hydroxy-3-methylbutyric acid benzhydryl ester 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 氢气 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 44.17h， 生成 (S)-2-[(R)-3-(3-tert-Butoxycarbonylamino-propionyloxy)-2,2-dimethyl-oct-7-ynoylamino]-3-methyl-butyric acid (S)-1-[((R)-1-tert-butoxycarbonyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-methyl-propyl ester
  参考文献：
  名称：

  The Total Synthesis and Stereochemical Revision of Yanucamide A

  摘要：

  GraphicsThe first total synthesis of yanucamide A is reported via amide and ester couplings of the key components. This synthesis has established the configuration at the previously ambiguous 3-position, and also revised the stereochemistry at the 22-position, to give 3S, 12S, 17S, 22S for the natural product.

  DOI：

  10.1021/ol034803d
• 作为产物：
  描述：

  L-缬氨酸 在 碘苯二乙酸 、 硫酸 、 碘 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (S)-2-hydroxy-3-methylbutyric acid benzhydryl ester
  参考文献：
  名称：

  Stereocontrolled Synthesis of Onchidins

  摘要：

  (GRAPHICS)The first total synthesis of a molecule possessing the stereochemistry proposed for onchidin is described. The structure synthesized appears to be different from that of the marine natural product.

  DOI：

  10.1021/ol048437p

文献信息

• Stereoselective synthesis of multiply substituted [1,2]oxazinan-3-ones via ring-closing metathesis
  作者：Gennady V Shustov、Melanie K Chandler、Saul Wolfe

  DOI：10.1139/v04-174

  日期：2005.2.1

  The title compounds are α-amino acids whose nitrogen atoms are enclosed within 4,5-disubstituted, six-membered cyclic hydroxamates and they are of interest as potential β-lactam surrogates. The compounds have been synthesized in the present work by functionalization of the double bonds of N-substituted 6H-[1,2]oxazin-3-ones, which are obtained upon successive reaction of the triflates of S-α-hydroxy esters with O-allylhydroxylamine and acryloyl chloride, followed by cyclization of the resulting R-α-N-acryloyl-N-allyloxyamino esters in the presence of the ring-closing metathesis (RCM) catalyst bis(tricyclohexylphosphine)benzylideneruthenium dichloride. The olefins are also accessible, but less efficiently so, by a Wittig sequence that employs bromoacetyl bromide in place of acryloyl chloride, followed successively by triphenylphosphine, silver triflate, ozonolysis, and cyclization. Asymmetric dihydroxylation of these chiral olefins affords a single diastereomer in high yield having either the αR,4S,5S- or the αR,4R,5R configuration, depending on the auxiliary. The configuration of the αR,4R,5R isomer has been confirmed by its conversion to (αR,4S,5R)-2-(α-carboxyethyl)-4-phenylacetylamino-5-hydroxy-1,2-oxazinan-3-one, whose αR,4R,5S diastereomer was previously prepared from L-ascorbic acid. With N-bromosuccinimide in aqueous dimethylformamide, a 6H-[1,2]oxazin-3-one afforded a separable 1:1 mixture of bromohydrins, which could be cyclized to epoxides or hydrogenolyzed to 5-hydroxy-1,2-oxazinan-3-ones. Key words: penicillin surrogates, asymmetric dihydroxylation, bis(tricyclohexylphosphine)benzylideneruthenium dichloride, cyclic sulfite, epoxides, azidohydrin, bromohydrin.

  这些标题化合物是α-氨基酸，其氮原子被包含在4,5-二取代的六元环羟肟内，它们具有潜在的β-内酰胺替代物的兴趣。这些化合物在本研究中通过N-取代6H-[1,2]噁唑-3-酮的双键官能化合成，该噁唑-3-酮是通过连续反应S-α-羟基酯的三氟甲烷酸酯与O-烯丙基羟胺和丙烯酰氯得到的，随后在环戊烯烃闭环甲硫醚催化剂双(三环己基膦)苯基亚铑二氯化物存在下，通过得到的R-α-N-丙烯酰-N-烯丙基氧基氨基酯的环化来实现。烯烃也可以通过Wittig序列获得，但效率较低，该序列使用溴乙酰溴代替丙烯酰氯，然后依次经过三苯基膦、三氟乙酸银、臭氧化、环化反应。这些手性烯烃的不对称二羟基化反应产生高产率的单对映体，具有αR,4S,5S-或αR,4R,5R构型，取决于辅助剂。αR,4R,5R异构体的构型已通过其转化为(αR,4S,5R)-2-(α-羧乙基)-4-苯乙酰氨基-5-羟基-1,2-噁唑烷-3-酮来确认，其αR,4R,5S对映体之前是由L-抗坏血酸制备的。在水合二甲基甲酰胺中使用N-溴代琥珀酰亚胺，6H-[1,2]噁唑-3-酮产生可分离的溴水合物1:1混合物，可被环化为环氧化物或氢解为5-羟基-1,2-噁唑烷-3-酮。关键词：青霉素替代物、不对称二羟基化、双(三环己基膦)苯基亚铑二氯化物、环磺酸酯、环氧化物、叠氮水合物、溴水合物。
• Oxazinones and methods for their use and synthesis
  申请人：Wolfe Saul

  公开号：US20050124612A1

  公开（公告）日：2005-06-09

  The invention pertains, at least in part, to new intermediates and synthetic methods for the stereospecific synthesis of oxazinone compounds, which are useful, for example, as antibiotics. The invention also pertains to novel olefinic oxazinone compounds, methods for their synthesis, and methods of using these compounds for the synthesis of oxazinones. The invention also pertains to methods for using the compounds to treat bacterial associated states in subjects.

  本发明至少涉及新的中间体和合成方法，用于立体选择性合成噁唑烷酮化合物，该化合物可用作抗生素等。本发明还涉及新颖的烯烃噁唑烷酮化合物，其合成方法以及使用这些化合物合成噁唑烷酮的方法。本发明还涉及使用这些化合物治疗受细菌感染的患者的方法。
• Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria
  作者：Fangjun Liu、Qunhuan Kou、Hongyuan Li、Yangzhi Cao、Meng Chen、Xin Meng、Yinyong Zhang、Ting Wang、Hui Wang、Dan Zhang、Yushe Yang

  DOI：10.1021/acs.jmedchem.4c00265

  日期：2024.4.25

  cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against Klebsiella pneumoniae and Acinetobacter baumannii, intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized

  头孢地可是第一个被批准的针对多重耐药革兰氏阴性菌的儿茶酚缀合头孢菌素，但其应用受到吡咯烷连接子化学稳定性差、对肺炎克雷伯菌和鲍曼不动杆菌效力中等、盐制备过程复杂以及潜在潜力的限制。超敏反应。为了解决这些问题，设计、合成和评估了一系列新型儿茶酚共轭衍生物。进行了广泛的结构-活性关系和结构-代谢关系（SMR），发现了具有新硫醚连接基的有前途的化合物86b （代码号YFJ-36）。与头孢地考相比， 86b表现出优异的广谱体外抗菌活性，尤其是针对鲍曼不动杆菌和肺炎克雷伯菌。在小鼠全身感染模型中观察到有效的体内功效。此外， 86b在 pH 6-8 的流体介质中的物理化学稳定性得到增强。由于季铵连接基， 86b还降低了潜在的过敏风险。 86b的改进性能支持了其进一步的研究和开发。
• EP4159733
  申请人：——

  公开号：——

  公开（公告）日：——
• US6861416B2
  申请人：——

  公开号：US6861416B2

  公开（公告）日：2005-03-01