(R)-异丝氨酸 | 632-11-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丝氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (R)-异丝氨酸
• 英文名称: (R)-isoserine
• 英文别名: (R)-3-amino-2-hydroxypropanoic acid；(2R)-isoserine；isoserine；D-isoserine；D-iSer；(2R)-3-amino-2-hydroxypropanoic acid
• CAS: 632-11-1
• 化学式: C₃H₇NO₃
• 分子量: 105.093
• InChiKey: BMYNFMYTOJXKLE-UWTATZPHSA-N

物化性质

• 熔点：
  197-198 °C
• 沸点：
  386.6±27.0 °C(Predicted)
• 密度：
  1.415±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

制备方法

(S)-异丝氨酸是一种具有生物活性的β-氨基酸和重要的医药中间体。

用途简介与用途

(S)-异丝氨酸是一种具有生物活性的β-氨基酸，也是重要的医药中间体。

反应信息

• 作为反应物：
  描述：

  2,5-二甲氧基四氢呋喃 、 (R)-异丝氨酸 在 sodium acetate 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 2.5h， 生成 (R)-2-hydroxy-3-(1H-pyrrol-1-yl)propionic acid
  参考文献：
  名称：

  噻吩并嘧啶类衍生物、其制备方法及其在医药 上的应用

  摘要：

  本发明涉及噻吩并嘧啶类衍生物、其制备方法及其在医药上的应用。具体而言，本发明涉及一种通式(I)所示的噻吩并嘧啶类衍生物、其制备方法及含有该衍生物的药物组合物以及其作为治疗剂，特别是作为MCL‑1抑制剂的用途，其中通式(I)的各取代基与说明书中的定义相同。

  公开号：

  CN111187277B
• 作为产物：
  描述：

  (R)-3-benzyloxycarbonylamino-2-hydroxypropionic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 以92%的产率得到(R)-异丝氨酸
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599

文献信息

• SCOTfluors: Small, Conjugatable, Orthogonal, and Tunable Fluorophores for In Vivo Imaging of Cell Metabolism
  作者：Sam Benson、Antonio Fernandez、Nicole D. Barth、Fabio de Moliner、Mathew H. Horrocks、C. Simon Herrington、Jose Luis Abad、Antonio Delgado、Lisa Kelly、Ziyuan Chang、Yi Feng、Miyako Nishiura、Yuichiro Hori、Kazuya Kikuchi、Marc Vendrell

  DOI：10.1002/anie.201900465

  日期：2019.5.20

  of live cells. However, in situ metabolic imaging studies are hampered by the lack of fluorescent chemical structures that allow direct monitoring of small metabolites under physiological conditions with high spatial and temporal resolution. Herein, we describe SCOTfluors as novel small-sized multi-colored fluorophores for real-time tracking of essential metabolites in live cells and in vivo and for

  代谢物的运输和运输对于活细胞的正常运行至关重要。但是，由于缺乏荧光化学结构，因此无法在生理条件下以高时空分辨率直接监测小代谢物，就无法进行原位代谢成像研究。在这里，我们将SCOTfluors描述为新颖的小型多色荧光团，用于实时跟踪活细胞和体内的必需代谢产物，以及从可变起源的人类癌细胞中获取代谢谱。
• A total synthesis of nocardicins
  作者：H.P. Isenring、W. Hofheinz

  DOI：10.1016/s0040-4020(01)92152-0

  日期：1983.1

  ring system which was transformed in 4 steps into 3-aminonocardicinic acid. A protected side chain of nocardicin D was synthesized from d-asparagine in 6 steps. Coupling of these units and further conversion to nocardicins A, B and D followed published procedures. Using l-asparagine for the synthesis of the side chain led to unnatural isonocardicin A. Biological activities of the products are compared

  d-异丝氨酸或l-异丝氨酸，二苯基甲基异氰化物和对-（苄氧基）苯甲醛的四组分缩合被用于构建官能化的β-内酰胺环系统，该系统以4个步骤转化为3-氨基心酸。由d-天冬酰胺分6步合成诺卡替丁D的保护侧链。遵循已公布的程序，将这些单元偶联并进一步转化为诺卡汀A，B和D。使用l-天冬酰胺来合成侧链会导致非天然的异心卡那霉素A。比较了产品的生物活性。
• Synthesis of fluorescent and biotinylated analogues of (1R, 2S, 3R)-2-acetyl-4(5)-(1,2,3,4-Tetrahydroxybutyl)imidazole
  作者：Alison T Ung、Stephen G Pyne

  DOI：10.1016/0040-4039(96)01325-1

  日期：1996.8

  A method for preparing fluorescent and biotinylated analogues of the biologically active compound (1R, 2S, 3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole 1 is reported.

  报道了一种制备生物活性化合物（1 R，2 S，3 R）-2-乙酰基-4（5）-（1,2,3,4-四羟基丁基）咪唑1的荧光和生物素化类似物的方法。
• Efficient syntheses of enantiomerically pure L and D-allothreonines and (S) and (R) isoserines
  作者：Dominique Pons、Monique Savignac、Jean-Pierre Genet

  DOI：10.1016/s0040-4039(00)97795-5

  日期：1990.1

  Both enantiomers of (S) and (R) isoserine as well (D) and (L) allothreonine are prepared optically pure in three steps by asymmetric Sharpless epoxidation of crotyl and allylic alcohols into - followed by an improved RuCl3/NaIO4/water oxidation procedure to low molecular weight glycidic acids and epoxide opening by ammonia with (20 – 33%) overall yields.

  （S）和（R）异丝氨酸的对映体以及（D）和（L）别甲苏氨酸都是通过三步光学纯化的，方法是将巴豆基和烯丙醇的不对称Sharpless环氧化为-然后是经过改进的RuCl 3 / NaIO 4 /水氧化过程可制得低分子量的缩水甘油酸，氨气可将环氧化合物打开，总收率为（20％-33％）。
• Design and Synthesis of Sulfur Based Inhibitors of Matrix Metalloproteinase-1.
  作者：Tetsunori Fujisawa、Shinjiro Odake、Yuji Ogawa、Junko Yasuda、Yasuo Morita、Tadanori Morikawa

  DOI：10.1248/cpb.50.239

  日期：——

  Fibroblast collagenase (MMP-1), a member of the matrix metalloproteinases family, is believed to be a pathogenesis of arthritis, by cleaving triple-helical type II collagen in cartilage. From the similarity of the active site zinc binding mode with hydroxamate, we designed and synthesized α-mercaptocarbonyl possessing compounds (3—5), which incorporated various peptide sequences as enzyme recognition sites. The P4–P1 peptide incorporating compound (3) exhibited as potent inhibition as the hydroxamate (1) and the carboxylate (2) type inhibitors, with an IC50 of 10−6 M order against MMP-1. But the inhibitor (3) related compounds (6—8) displayed decreased or no inhibitory potencies. These results suggest that the existence of both the carbonyl and thiol groups might be critical for the inhibition, and the distance between the two functional groups is important for inhibitory potency. For Pn′ peptide incorporating compounds (4a—k), except for 4h and 4k, all compounds showed IC50 values under sub-nanomolar. Among them, for potent inhibition, Leu was better than Phe and Val as the P1′ amino acid, and the P2′ position amino acid was necessary, and preferentially Phe. Insertion of the Pn peptide into 4d or 4k, giving compounds 5a—c, did not increase the activities of 4d and 4k. Substitution of the mercapto group with other functional groups lost the activity of compound 4a. The stereochemical preference at the thiol-attached position was also determined by preparation of both isomers of 4a. It was found that the S configuration compound (36b) is approximately 100 times more potent than the corresponding R-isomer (36a).

  成纤维细胞胶原酶（MMP-1）是基质金属蛋白酶家族的一员，被认为是关节炎的病理机制之一，它通过切割软骨中的三重螺旋II型胶原蛋白发挥作用。基于其活性位点锌结合模式与羟肟酸的相似性，我们设计并合成了含有α-巯基羰基的化合物（3—5），这些化合物包含了作为酶识别位点的不同肽序列。包含P4–P1肽的化合物（3）表现出与羟肟酸（1）和羧酸（2）类型抑制剂相当的强抑制作用，对MMP-1的IC50值为10−6小于M的量级。然而，与抑制剂（3）相关的化合物（6—8）显示出下降或无抑制活性。这些结果表明，羰基和巯基的共存可能对抑制作用至关重要，并且这两个官能团之间的距离对抑制效能也很重要。对于Pn'肽的包含化合物（4a—k），除了4h和4k以外，所有化合物的IC50值均低于亚纳摩尔。其中，在强抑制作用方面，Leu作为P1'氨基酸优于Phe和Val，而P2'位的氨基酸是必要的，并且优先选择Phe。将Pn肽插入4d或4k生成化合物5a—c，并未增加4d和4k的活性。将巯基替换为其他官能团则失去了化合物4a的活性。通过合成4a的两种异构体还确定了在巯基连接位置的立体化学偏好，发现S构型的化合物（36b）的效能约为相应R-异构体（36a）的100倍。