D-tert-Leucine tert-butyl ester | 61169-85-5

• 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: D-tert-Leucine tert-butyl ester
• 英文别名: 3-Methyl-D-valine tert-butyl ester；tert-butyl (2R)-2-amino-3,3-dimethylbutanoate
• CAS: 61169-85-5
• 化学式: C₁₀H₂₁NO₂
• 分子量: 187.282
• InChiKey: IGZORTGLYQDNMF-ZETCQYMHSA-N

物化性质

• 沸点：
  90-91 °C(Press: 21 Torr)
• 密度：
  0.930±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2922499990

反应信息

• 作为反应物：
  描述：

  D-tert-Leucine tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 三乙基硅烷 、 水 、 potassium carbonate 、 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-N-hydroxy-3,3-dimethyl-2-[(3-methyl-butyl)-(naphthalene-2-sulfonyl)-amino]-butyramide
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087
• 作为产物：
  描述：

  D-叔亮氨酸 、 叔丁醇 以62%的产率得到
  参考文献：
  名称：

  HASHIMOTO S.; YAMADA S.; KOGA K., CHEM. AND PHARM. BULL., 1979, 27, NO 3, 771-782

  摘要：

  DOI：

文献信息

• Total Synthesis of (-)-Silphiperfol-6-ene and (-)-Methyl Cantabradienate
  作者：Nha Huu Vo、Barry B. Snider

  DOI：10.1021/jo00097a053

  日期：1994.9

  (-)-Silphiperfol-6-ene (10) and (-)-methyl cantabradienate (11) have been prepared in seven steps from (R)-3-methyl-1-cyclopentenecarboxaldehyde in 13 and 9% overall yield, respectively. Addition of isopentenylmagnesium bromide to imine 22 afforded 65% of aldehyde 14. Oxidation provided acid 15, which was converted to ketene 20, which underwent an intramolecular [2 + 2] cycloaddition to afford cyclobutanone 13. Mn(III)-based oxidative fragmentation-cyclization of ethynyl cyclobutanol 25 provided an efficient route to the key methylenecyclopentanone 12. Addition of methyllithium and Birch reduction completed the synthesis of (-)-silphiperfol-6-ene 10. Formation of dienyl triflate 29 and palladium-catalyzed carbonylation concluded the first synthesis of (-)methyl cantabradienate (11).

  (-)-Silphiperfol-6-ene (10) 和 (-)-甲基cantabradienate (11) 已经通过从(R)-3-甲基-1-环戊烯羧酸仿开始的七步反应制备而成，总产率分别为13%和9%。将异戊烯基溴化镁加成到亚胺22中，获得了65%的醛14。氧化提供了酸15，将其转化为酮烯20，随后酮烯20通过分子内[2 + 2]环加成反应生成环丁酮13。以Mn(III)为基础的氧化断裂环化反应处理乙烯基环丁醇25，为制备关键的甲基环戊酮12提供了一条高效途径。甲基锂的加成和Birch还原完成了(-)-silphiperfol-6-ene 10的合成。二烯基三氟乙酸酯29的形成以及钯催化的羰基化反应，标志着(-)-甲基cantabradienate (11) 的首次合成。
• ANTIVIRAL COMPOUNDS
  申请人：Cai Zhenhong R.

  公开号：US20110135599A1

  公开（公告）日：2011-06-09

  The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

  本申请包括HCV的新型抑制剂，含有这些化合物的组合物，以及包括这些化合物的给药的治疗方法。
• Stereoselective reactions. I. A highly efficient asymmetric synthesis of .BETA.-substituted aldehydes via 1,4-addition of Grignard reagents to optically active .ALPHA.,.BETA.-unsaturated aldimines.
  作者：SHUNICHI HASHIMOTO、SHUNICHI YAMADA、KENJI KOGA

  DOI：10.1248/cpb.27.771

  日期：——

  The 1, 4-addition of Grignard reagents to the chiral α, β-unsaturated aldimines (3d, e), prepared from α, β-unsaturated aldehydes (1) and optically active tert-leucine tert-butyl ester (2d), afforded, after hydrolysis, optically active β-substituted aldehydes (4) in 91-98% enantiomeric excess. The present method has advantages in giving aldehydes (4) in high enantiomeric purities, allowing easy preparation of the aldimines as well as easy recovery of optically active tert-leucine tert-butyl ester (2d) without any racemization for reuse, and exhibiting general utility. The possible mechanism of the reaction, by which the absolute configuration of the aldehydes (4) is unequivocally predictable, is proposed.

  格里尼亚尔试剂对手性α, β-不饱和醛亚胺（3d, e）的1, 4-加成反应，是通过α, β-不饱和醛（1）和光学活性的tert-亮氨酸tert-丁基酯（2d）制备的，经过水解后获得了光学活性的β-取代醛（4），其对映体过量为91-98%。该方法在提供高对映体纯度的醛（4）方面具有优势，能够简便地制备醛亚胺，并且能够轻松回收光学活性的tert-亮氨酸tert-丁基酯（2d），而不会发生消光，从而可重复使用，且具有广泛的适用性。提出了该反应的可能机制，通过该机制，可以明确预测醛（4）的绝对构型。
• Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines
  作者：Paul V. Fish、Christopher G. Barber、David G. Brown、Richard Butt、Michael G. Collis、Roger P. Dickinson、Brian T. Henry、Valerie A. Horne、John P. Huggins、Elizabeth King、Margaret O'Gara、Dawn McCleverty、Fraser McIntosh、Christopher Phillips、Robert Webster

  DOI：10.1021/jm061066t

  日期：2007.5.1

  1-isoquinolinylguanidines were previously disclosed as potent and selective inhibitors of urokinase-type plasminogen activator (uPA). Further investigation of this template has revealed that incorporation of a 7-sulfonamide group furnishes a new series of potent and highly selective uPA inhibitors. Potency and selectivity can be achieved with sulfonamides derived from a variety of amines and is further enhanced by the incorporation of sulfonamides derived from amino acids. The binding mode of these 1-isoquinolinylguanidines has been investigated by X-ray cocrystallization studies. uPA inhibitor 26 was selected for further evaluation based on its excellent enzyme potency (Ki 10 nM) and selectivity profile (4000-fold versus tPA and 2700-fold versus plasmin). In vitro, compound 26 is able to inhibit exogenous uPA in human chronic wound fluid (IC50=0.89 microM). In vivo, in a porcine acute excisional wound model, following topical delivery, compound 26 is able to penetrate into pig wounds and inhibit exogenous uPA activity with no adverse effect on wound healing parameters. On the basis of this profile, compound 26 (UK-371,804) was selected as a candidate for further preclinical evaluation for the treatment of chronic dermal ulcers.
• US8927484B2
  申请人：——

  公开号：US8927484B2

  公开（公告）日：2015-01-06