benzyl ((2S,3S)-1-(methoxy(methyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate | 147961-53-3

• 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: benzyl ((2S,3S)-1-(methoxy(methyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate
• 英文别名: benzyl N-[(2S,3S)-1-[methoxy(methyl)amino]-3-methyl-1-oxopentan-2-yl]carbamate
• CAS: 147961-53-3
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: SMZGSYKVMLTMDW-JSGCOSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl ((2S,3S)-1-(methoxy(methyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 3.5h， 生成 4-amino-3-methylundecan-5-ol
  参考文献：
  名称：

  Auxiliary Agents for the Peroral Administration of Peptide and Protein Drugs:  Synthesis and Evaluation of Novel Pepstatin Analogues

  摘要：

  The peroral administration of(poly)peptide drugs requires the development of delivery systems, which provide a protective effect toward a gastrointestinal enzymatic attack. A promising strategy for such systems represents polymer-enzyme inhibitor conjugates in which the embedded therapeutic agent is protected. However, the practical use of polymer-inhibitor conjugates has so far been limited by high production costs of these auxiliary agents. To solve this problem for delivery systems shielding from pepsinic degradation, structurally simplified analogues of the pepsin inhibitor pepstatin A have been synthesized. The synthesis of tripeptide analogues, described by McConnell et al., led us to pursue further modifications varying the C-terminus. Our target to attach a spacer moisty-enabling the free access of pepsin to the inhibitor-should be combined with an attractive synthetic approach providing low production costs in large-scale preparation. Structure modifications comprised either the side chain of the third amino acid which served as starting compound designing the C-terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link, simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory activities which have been evaluated by an enzyme assay were significantly dependent on the nature of the side chain, whereas the length of the spacer had no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl moiety as side chain displayed a strong inhibitory effect which was comparable to that pepstatin A. These congeners represent promising auxiliary agents for the peroral administration of(poly)peptide drugs.

  DOI：

  10.1021/jm980015w
• 作为产物：
  描述：

  N-苄氧羰基-L-异亮氨酸 、 二甲羟胺盐酸盐 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97%的产率得到benzyl ((2S,3S)-1-(methoxy(methyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate
  参考文献：
  名称：

  Matlystatins, new inhibitors of type IV collagenases from Actinomadura atramentaria. IV. Synthesis and structure-activity relationships of matlystatin b and its stereoisomers.

  摘要：

  首次全合成了 IV 型胶原酶的低分子量抑制剂 matlystatin B (1a)，并明确确定了其绝对构型。此外，合成了1a的十种立体异构体，并研究了每种立体异构体对92 kDa IV型胶原酶和其他金属蛋白酶的抑制作用。

  DOI：

  10.7164/antibiotics.47.1481

文献信息

• α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation
  作者：Joel F. Hooper、Sangwon Seo、Fiona R. Truscott、James D. Neuhaus、Michael C. Willis

  DOI：10.1021/jacs.5b11892

  日期：2016.2.10

  stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.

  容易获得的 α-氨基醛，在氮上结合了一个甲硫基甲基 (MTM) 保护基团，被证明是 Rh 催化的炔烃加氢酰化反应中的有效底物。反应在温和条件下进行，采用小咬角双膦配体，具有良好的官能团耐受性和高立体特异性。成功地使用了源自甘氨酸、丙氨酸、缬氨酸、亮氨酸、苯丙氨酸、异亮氨酸、丝氨酸、色氨酸、甲硫氨酸和半胱氨酸的氨基醛，以及源自苯乳酸的富含对映异构体的 α-OMTM-醛。α-氨基烯酮产物的合成效用在天然产物鞘氨醇的短对映选择性合成中得到证明。
• Stereoselective cyclopropanations of amino-acid derived enones
  作者：Avraz Anwar、Holli Kerns、Taylor Orr、Jonathan Byrd、Zackary Fitzsimonds、Norma Dunlap

  DOI：10.1016/j.tetlet.2020.152552

  日期：2020.11

  Stereoselective cyclopropanation of a series of amino acid-derived enones to afford cyclopropyl keto-esters is reported, using a Michael-induced ring closure. The use of quinine and quinidine ether catalysts in the cyclopropanation step afforded the cyclopropyl keto-esters with high stereoselectivity. Results follow a consistent pattern, with the pseudoenantiomeric catalysts leading to opposite stereoselectivity

  据报道，使用迈克尔诱导的闭环，一系列氨基酸衍生的烯酮的立体选择性环丙烷化以提供环丙基酮酯。在环丙烷化步骤中使用奎宁和奎尼丁醚催化剂提供了具有高立体选择性的环丙基酮酯。结果遵循一致的模式，假对映体催化剂导致相反的立体选择性，从而可以合成顺式或反式非对映异构体。
• Collagenase inhibitor
  申请人：Sankyo Company, Limited

  公开号：US05643908A1

  公开（公告）日：1997-07-01

  Compounds having inhibitory activity against inhibitory activity against type IV collagenase and are useful as angiogenesis, cancer infiltration or cancer metastasis inhibitors. The compounds have the formula: ##STR1## in which R.sup.1 represents a group of formula: --OR.sup.3 (wherein R.sup.3 represents a hydrogen atom or an alkyl group), --NR.sup.4 R.sup.5 (wherein R.sup.4 and R.sup.5 each represents a hydrogen atom, an alkyl or alkoxy group), --NHCH(R.sup.6 COR.sup.7 (wherein R.sup.6 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R.sup.7 represents an alkyl group), --NHCH(R.sup.6)COOR.sup.8 (wherein R.sup.8 represents an alkyl group) or --NHCH(R.sup.6)CONR.sup.9 R.sup.10 (wherein R.sup.9 and R.sup.10 each represents a hydrogen atom or an alkyl group, or NR.sup.9 R.sup.10 together represent a heterocyclic ring group); and R.sup.2 represents a hydrogen atom, an alkyl or aralkyl group.

  具有对抑制IV型胶原酶活性的化合物，可用作抑制血管生成、癌症浸润或癌症转移的抑制剂。这些化合物的化学式为：##STR1## 其中R.sup.1代表以下式的基团：--OR.sup.3（其中R.sup.3代表氢原子或烷基），--NR.sup.4 R.sup.5（其中R.sup.4和R.sup.5分别代表氢原子、烷基或烷氧基），--NHCH(R.sup.6 COR.sup.7（其中R.sup.6代表具有1至4个碳原子的氢原子或烷基，R.sup.7代表烷基），--NHCH(R.sup.6)COOR.sup.8（其中R.sup.8代表烷基）或--NHCH(R.sup.6)CONR.sup.9 R.sup.10（其中R.sup.9和R.sup.10各自代表氢原子或烷基，或NR.sup.9 R.sup.10一起代表杂环环基）；而R.sup.2代表氢原子、烷基或芳基烷基。
• Design of a Potent Combined Pseudopeptide Endothelin-A/Endothelin-B Receptor Antagonist, Ac-<scp>d</scp>Bhg¹⁶-Leu-Asp-Ile-[NMe]Ile-Trp²¹ (PD 156252):  Examination of Its Pharmacokinetic and Spectral Properties
  作者：Wayne L. Cody、John X. He、Michael D. Reily、Stephen J. Haleen、Donnelle M. Walker、Eric L. Reyner、Barbra H. Stewart、Annette M. Doherty

  DOI：10.1021/jm970161m

  日期：1997.7.1

  The endothelins (ETs) are a family of bicyclic 21-amino acid peptides that are potent and prolonged vasoconstrictors. It has been shown that highly potent combined ETA/ETB receptor antagonists can be developed from the C-terminal hexapeptide of ET (His(16)-Leu(17)-Asp(18)-Ile(19)-Ile(20)-Trp(21)), such as Ac-DDip(16)-Leu-Asp-Ile-Ile-Trp(21) (PD 142893) and Ac-DBhg(16)-Leu-Asp-Ile-Ile-Trp(21) (PD 145065). However, these compounds are relatively unstable to enzymatic proteolysis as determined in an in vitro rat intestinal perfusate assay. This instability is thought to be due to carboxypeptidase activity. In fact, incubation of PD 145065 with carboxypeptidase inhibitors greatly increased its half-life in rat intestinal perfusate. By performing a reduced amide bond and N-methyl amino acid scan, it was discovered that N-methylation of Ile(20) resulted in a compound (Ac-DBhg(16)-Leu-Asp-Ile-[NMe]Ile-Trp(21), PD 156252) that retained full receptor affinity at both endothelin receptor subtypes along with enhanced proteolytic stability and cellular permeability. Interestingly, N-methylation of this bond allows the cis configuration to be readily accessible which greatly alters the preferred structure of the entire molecule and may be responsible for the observed enhanced metabolic stability.
• Synthesis and determination of the absolute configuration of matlystatin B
  作者：Kazuhiko Tamika、Takeshi Ogita、Kazuhiko Tanzawa、Yukio Sugimura

  DOI：10.1016/s0040-4039(00)61652-0

  日期：1993.1