(3S,4S)-4-(carbamic acid benzyl ester)-3-hydroxy-6-methyl-heptanoic acid | 93287-37-7

• 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
• 英文名称: (3S,4S)-4-(carbamic acid benzyl ester)-3-hydroxy-6-methyl-heptanoic acid
• 英文别名: N-(Benzyloxycarbonyl)statine；N-benzyloxycarbonyl statine；Z-syn-statine；Z-Sta-OH；(3S,4S)-3-hydroxy-6-methyl-4-(phenylmethoxycarbonylamino)heptanoic acid
• CAS: 93287-37-7
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: KVOCLJKQNJNTDY-KBPBESRZSA-N

物化性质

• 熔点：
  118-121 °C(Solv: hexane (110-54-3); ethyl ether (60-29-7))
• 沸点：
  521.2±50.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-(carbamic acid benzyl ester)-3-hydroxy-6-methyl-heptanoic acid 在 吡啶 、 盐酸 、 sodium tetrahydroborate 、 potassium tert-butylate 、 对甲苯磺酸 、 二甲基亚砜 作用下， 以 乙醇 、 苯 为溶剂， 反应 51.17h， 生成 (4S,5S)-3-Benzyloxycarbonyl-5-ethenyl-4-isobutyl-2,2-dimethyloxazolidine
  参考文献：
  名称：

  在其N-末端结合亚砜等排体的含高抑素的肾素抑制剂的合成

  摘要：

  以天然他汀为原料合成了一种高抑素类似物 (2RS,4S,5S)N-isobutyl-5-amino-2-ethyl-4-hydroxy-7-methyloctanamide。(4S,5R)-3-benzyloxycarbonyl-5-formyl-4-isobutyl-2,2-二甲基恶唑烷的改良 Horner-Wadsworth-Emmons 反应是合成高抑素类似物的关键反应。N-末端前体的立体选择性和立体特异性合成，N-[(2R)-3-羟基-2-(1-萘基甲基)丙酰基]-L-正亮氨酸叔丁酯和高活性肾素抑制剂的全合成， (2RS,4S,5S)-N-isobutyl-5-[[N-[(2S)-2-(1-naphthylmethyl)-3-(2-pyrimidinylsulfonyl)propionyl]-L-norleucyl]amino]-2-描述了乙基-4-羟基-7-甲基辛酰胺。

  DOI：

  10.1246/bcsj.63.2224
• 作为产物：
  描述：

  N-carbobenzoxy-L-leucinal 在 18-冠醚-6 、 铂 氧气 、 双(三甲基硅烷基)氨基钾 、 二异丁基氢化铝 、 碳酸氢钠 、 间氯过氧苯甲酸 、 红铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (3S,4S)-4-(carbamic acid benzyl ester)-3-hydroxy-6-methyl-heptanoic acid
  参考文献：
  名称：

  非对映选择性环氧化顺式-4-氨基烯丙基醇与米氯过苯甲酸。他汀的有效合成

  摘要：

  广志弘

  DOI：

  10.1039/c39870000311

文献信息

• Synthesis of chiral urethane N-alkoxycarbonyl tetramic acids from urethane N-carboxyanhydrides (UNCAs)
  作者：Jean-Alain Fehrentz、Elisabeth Bourdel、Jean-Christophe Califano、Olivier Chaloin、Chantal Devin、Patrick Garrouste、Ana-Christina Lima-Leite、Muriel Llinares、François Rieunier、Jean Vizavonna、François Winternitz、Albert Loffet、Jean Martinez

  DOI：10.1016/s0040-4039(00)76757-8

  日期：1994.3

  The synthesis of chiral N-protected tetramic acid derivatives which are important precursors of β-hydroxy γ-amino acid under mild conditions is described. Reaction of urethane-N-carboxyanhydrides (UNCAs) with Meldrum's acid in the presence of a tertiary amine, followed by subsequent cyclisation produced tetramic acid derivatives. This procedure is applicable to Boc-, Fmoc- and Z- N-carboxyanhydrides

  描述了在温和条件下手性N-保护的四酸衍生物的合成，该衍生物是β-羟基γ-氨基酸的重要前体。在叔胺存在下，氨基甲酸酯-N-羧基酐（UNCA）与Meldrum酸反应，然后环化生成四甲酸衍生物。此程序适用于Boc-，Fmoc-和Z- N-羧基酸酐。
• Substituted tetrapeptides
  申请人：Ciba-Geigy Corporation

  公开号：US04595677A1

  公开（公告）日：1986-06-17

  Tetrapeptides of the formula I, ##STR1## in which R.sup.1 represents hydrogen or acyl, R.sup.2 represents alkyl or aralkyl, R.sup.3 represents free or functionally modified hydroxy, R.sup.4 represents free or substituted amino or free or etherified hydroxy, and -Pro-, -Phe- and -His- respectively represent the bivalent radicals of the amino acids proline, phenylalanine and histidine or the (D)-isomers thereof, salts of such compounds having salt-forming groups, and processes for their manufacture. The compounds inhibit the action of the enzyme renin and can be used as antihypertensives and for the treatment of cardiac insufficiency.

  公式I的四肽，其中R.sup.1代表氢或酰基，R.sup.2代表烷基或芳基烷基，R.sup.3代表自由或功能性修饰的羟基，R.sup.4代表自由或取代氨基或自由或醚化羟基，-Pro-，-Phe-和-His-分别代表脯氨酸，苯丙氨酸和组氨酸的二价基团或其(D)异构体，具有形成盐的基团的这些化合物的盐以及它们的制造过程。这些化合物抑制酶肾素的作用，可用作降压剂和治疗心力衰竭。
• 5-Substituted amino-4-hydroxy-pentanoic acid derivatives and their use
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：EP0264106A2

  公开（公告）日：1988-04-20

  A 5-substituted amino-4-hydroxy-pentanoic acid derivative having the formula: wherein R¹ is a hydrogen atom, a lower alkoxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group or a lower alkanoyl group which may be substituted by from one to three substituents selected from the group consisting of an amino group, a hydroxyl group, a carboxyl group, an aryloxy group, an aralkyloxycarbonylamino group, a lower alkoxycarbonylamino group wherein each of X¹ and X² which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, or X¹ and X² form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hereto atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom which may further contain a double bond in its carbon chain, each of R², R³ and R⁵ which may be the same or different is a hydrogen atom, a lower alkyl group or a residue of an acidic, neutral or basic amino acid, R⁴ is a hydrogen atom or a lower alkyl group, R⁶ is a lower alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group which is substituted by one or two hydroxyl groups, R⁷ is a hydroxyl group, a -OY group wherein Y is a lower alkyl group, an aryl group, an aralkyl group, a lower alkoxyalkyl group, a lower alkanoyloxyalkyl group, a lower alkoxycarbonyloxyalkyl group or a 1-phthalidyl group, wherein each of Y¹ and Y² which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group or a cycloalkyl group, or Y¹ and Y² form together with the adjacent nitrogen atom 5- or 5-membered heterocyclic group which may further contain a hereto atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and each of n and m which may be the same or different is 0 or 1.

  5-取代氨基-4-羟基戊酸衍生物，其式如下 其中 R¹为氢原子、低级烷氧基羰基、芳氧基羰基、芳烷氧基羰基或低级烷酰基，该低级烷酰基可被选自氨基、羟基、羧基、芳氧基、芳烷氧基羰基氨基、低级烷氧基羰基氨基所组成的组中的一至三个取代基所取代 其中 X¹ 和 X² 可相同或不同，各自为氢原子、低级烷基、芳基或芳烷基，或 X¹ 和 X² 与邻近的氮原子一起形成 5 或 6 元杂环基团，该杂环基团可进一步包含一个从氮原子、氧原子和硫原子组成的组中选出的同族原子，该杂环基团可进一步在其碳链中包含一个双键，R²、R³ 和 R⁵ 可相同或不同，各自为氢原子、R⁴ 是氢原子或低级烷基，R⁶ 是被一个或两个羟基取代的低级烷基、环烷基、环烷基烷基或芳烷基、R⁷ 是羟基、-OY 基团，其中 Y 是低级烷基、芳基、芳烷基、低级烷氧基烷基、低级烷酰氧基烷基、低级烷氧羰氧基烷基或 1-邻苯二甲酰基、 其中Y¹和Y²可以相同或不同，各自为氢原子、低级烷基、芳基、芳烷基或环烷基，或Y¹和Y²与相邻的氮原子一起形成5元或5元杂环基团，该杂环基团可进一步包含一个从氮原子、氧原子和硫原子组成的组中选出的同位原子，且n和m可以相同或不同，各自为0或1。
• Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond
  作者：Mark C. Allen、Walter Fuhrer、Brian Tuck、Roy Wade、Jeanette M. Wood

  DOI：10.1021/jm00127a041

  日期：1989.7

  The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.
• Synthesis of (+)- and (−)-Statine via Chiral Sulfoxide Chemistry
  作者：Cristina Pesenti、Pierfrancesco Bravo、Eleonora Corradi、Massimo Frigerio、Stefano V. Meille、Walter Panzeri、Fiorenza Viani、Matteo Zanda

  DOI：10.1021/jo010383z

  日期：2001.8.1