2-甲酰胺基-2-甲基-4-戊烯酸甲酯 | 142653-90-5

• 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
• 中文名称: 2-甲酰胺基-2-甲基-4-戊烯酸甲酯
• 英文名称: methyl 2-(formylamino)-2-methyl-4-pentenoate
• 英文别名: 2-formamido-2-methyl-4-pentenoic acid methyl ester；DL-formyl-α-methyl-α-allylglycine-OMe；Methyl 2-formamido-2-methylpent-4-enoate
• CAS: 142653-90-5
• 化学式: C₈H₁₃NO₃
• 分子量: 171.196
• InChiKey: HHJBOQRATGJYIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲酰胺基-2-甲基-4-戊烯酸甲酯 在 盐酸 作用下， 反应 18.0h， 以100%的产率得到2-amino-2-methyl-4-pentenoic acid hydrochloride
  参考文献：
  名称：

  Synthesis of .alpha.-substituted .alpha.-amino acids via cationic intermediates

  摘要：

  A novel synthetic approach to racemic alpha-substituted alpha-amino acids is described. The key intermediates of this methodology are highly electrophilic iminium ions, bearing carbonyl substituents at both the iminium carbon and nitrogen atom. The preparation of precursors 8, 10a-c, and 12 includes electrochemical oxidation techniques according to literature procedures. When an alpha-methyl precursor (8 or 10a) was used, reactions with allylsilanes and silyl enol ethers led to the desired products, but elimination to dehydroalanine derivatives appeared to be an important side reaction. A major improvement in the yields of the desired products could be effected by using longer reaction times. In this way, efficient syntheses of protected alpha-methyl-alpha-amino acids could be developed. The elimination process appeared to be a more serious problem in the alpha-benzyl (10b) and alpha-allyl (10c) cases. On the other hand, the alpha-phenyl precursor 12 appeared to be highly useful, because the elimination is impossible in this case. High yields of alpha-phenyl-alpha-amino acid derivatives were obtained upon reaction of 12 with silicon-activated pi-nucleophiles. Deprotection led to various types of free alpha-substituted alpha-amino acids.

  DOI：

  10.1021/jo00064a011
• 作为产物：
  描述：

  C^α-methyl-D,L-allylglycinamide 在 氯化亚砜 、 乙酸酐 作用下， 以 甲醇 、 甲酸 为溶剂， 反应 38.0h， 生成 2-甲酰胺基-2-甲基-4-戊烯酸甲酯
  参考文献：
  名称：

  跨复分解路线的功能化的α-甲基α-取代的氨基酸

  摘要：

  用化学酶方法合成功能化的α-甲基α-取代的氨基酸。这涉及酰胺酶介导的α-甲基α-取代的侧链ω-不饱和氨基酸的酶促拆分，然后通过交叉复分解进行功能化。

  DOI：

  10.1002/adsc.200600446

文献信息

• [EN] METATHESIS REACTION INVOLVING THE UNSATURATED SIDE CHAIN OF AN ALPHA, ALPHA-DISUBSTITUTED AMINO ACID<br/>[FR] REACTION DE METATHESE FAISANT APPEL A LA CHAINE LATERALE INSATUREE D'UN ACIDE AMINE ALPHA, ALPHA-DISUBSTITUE
  申请人：DSM IP ASSETS BV

  公开号：WO2004101476A1

  公开（公告）日：2004-11-25

  The invention relates to a process for amino acid synthesis, i.e., the preparation of side chain unsaturated α,α-disubstituted-α-amino acid derivatives with formula (1) wherein: * denotes a stereogenic C-atom PG represents an N-protecting group or the C-terminal part of an optionally protected amino acid or peptide chain; X represents an optionally substituted amine group or an alkoxy group; R1 represents an optionally substituted alkyl group; Ri represents R2 or R3; if Ri = R2 then Rii = R5 and if Ri = R3 then Rii = H; R2, R3 and R5 each independently represent H, an optionally substituted (cyclo)alkyl, (hetero)aryl, acyl, alkoxycarbonyl, cyano, di-alkylphosphonyl, oxiranyl group, a CHO group optionally protected as its acetal, or a group derived from an O-protected carbohydrate, or R2 and R5 may form together with the C-atorn to which they are attached an optionally substituted hydrocarbon ring, with the proviso that R2 , R3 and R5 do not all represent H at the same time. R4 represents H, an alkyl group or an aryl group; n represents an integer larger than or equal to 0, via a cross metathesis reaction between the corresponding amino acid derivative precursor and an (eventually substituted) alkene.

  该发明涉及一种氨基酸合成方法，即制备具有式（1）的侧链不饱和α，α-二取代-α-氨基酸衍生物的过程，其中：*表示一个立体异构的C原子，PG代表一个N保护基团或者一个可选择保护的氨基酸或肽链的C末端部分；X代表一个可选择取代的胺基团或者一个烷氧基团；R1代表一个可选择取代的烷基团；Ri代表R2或R3；如果Ri = R2，则Rii = R5，如果Ri = R3，则Rii = H；R2、R3和R5分别独立地代表H，一个可选择取代的（环）烷基，（杂环）芳基，酰基，烷氧羰基，氰基，二烷基膦基，环氧丙基基团，一个CHO基团，可选择保护为其缩醛基团，或者源自一个O保护的碳水化合物的基团，或者R2和R5可以与它们附着的C原子一起形成一个可选择取代的碳氢环，条件是R2、R3和R5不能同时代表H。R4代表H，一个烷基团或者一个芳基；n代表大于或等于0的整数，通过相应氨基酸衍生物前体与（可能取代的）烯烃之间的交叉甲醇反应。
• A Cross-Metathesis Route to Functionalized α-Methyl α-Substituted Amino Acids
  作者：Roy P. M. Storcken、Lavinia Panella、Floris L. van Delft、Bernard Kaptein、Quirinus B. Broxterman、Hans E. Schoemaker、Floris P. J. T. Rutjes

  DOI：10.1002/adsc.200600446

  日期：2007.1.8

  A chemoenzymatic approach to the synthesis of functionalized α-methyl α-substituted amino acids is detailed. This involves amidase-mediated enzymatic resolution of α-methyl α-substituted side-chain ω-unsaturated amino acids followed by functionalization via cross-metathesis.

  用化学酶方法合成功能化的α-甲基α-取代的氨基酸。这涉及酰胺酶介导的α-甲基α-取代的侧链ω-不饱和氨基酸的酶促拆分，然后通过交叉复分解进行功能化。
• Synthesis of .alpha.-substituted .alpha.-amino acids via cationic intermediates
  作者：Eric C. Roos、M. Carmen Lopez、Michael A. Brook、Henk Hiemstra、W. Nico Speckamp、Bernard Kaptein、Johan Kamphuis、Hans E. Schoemaker

  DOI：10.1021/jo00064a011

  日期：1993.6

  A novel synthetic approach to racemic alpha-substituted alpha-amino acids is described. The key intermediates of this methodology are highly electrophilic iminium ions, bearing carbonyl substituents at both the iminium carbon and nitrogen atom. The preparation of precursors 8, 10a-c, and 12 includes electrochemical oxidation techniques according to literature procedures. When an alpha-methyl precursor (8 or 10a) was used, reactions with allylsilanes and silyl enol ethers led to the desired products, but elimination to dehydroalanine derivatives appeared to be an important side reaction. A major improvement in the yields of the desired products could be effected by using longer reaction times. In this way, efficient syntheses of protected alpha-methyl-alpha-amino acids could be developed. The elimination process appeared to be a more serious problem in the alpha-benzyl (10b) and alpha-allyl (10c) cases. On the other hand, the alpha-phenyl precursor 12 appeared to be highly useful, because the elimination is impossible in this case. High yields of alpha-phenyl-alpha-amino acid derivatives were obtained upon reaction of 12 with silicon-activated pi-nucleophiles. Deprotection led to various types of free alpha-substituted alpha-amino acids.