tert-butyl (2S,3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)-2-hydroxybutanoate | 181137-51-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (2S,3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)-2-hydroxybutanoate
• 英文别名: tert-butyl (S,S,S)-2-hydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]butanoate；tert-butyl (2S,3S,αS)-2-hydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]butanoate；tert-butyl (2S,3S)-3-[benzyl-[(1S)-1-phenylethyl]amino]-2-hydroxybutanoate
• CAS: 181137-51-9
• 化学式: C₂₃H₃₁NO₃
• 分子量: 369.504
• InChiKey: JRBPZDZFCLSTDV-WFXMLNOXSA-N

物化性质

• 沸点：
  474.0±40.0 °C(Predicted)
• 密度：
  1.082±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)-2-hydroxybutanoate 在 palladium dihydroxide 氢气 、 甲烷 作用下， 以 甲醇 、 甲苯 为溶剂， 20.0 ℃ 、506.66 kPa 条件下， 反应 4.0h， 生成 tert-butyl (4S,5S)-4-methyloxazolidin-2-one-5-carboxylate
  参考文献：
  名称：

  抗-（2S，3S）-和顺-（2R，3S）-二氨基丁酸的不对称合成。

  摘要：

  将同手性N-苄基-N-α-甲基苄基氨基锂加到（E）-肉桂酸叔丁酯或（E）-巴豆酸叔丁酯中，并用叠氮化三苯胺原位胺化，仅形成相应的2-重氮大于95％de的-3-氨基酯 叔丁基（3S，alphaR）-3-N-苄基-N-α-甲基苄基氨基-3-苯基丙酸酯或叔丁基（3S，alphaS）-3-N-苄基-的（E）-烯醇锂的胺化N-α-甲基苄氨基氨基丁酸酯与三叠氮化物以良好的收率和85％的de和> 95％的de生成（2R，3R，alphaR）-和（2S，3S，alphaS）-抗-2-叠氮基-3-氨基酯分别。或者，可以将叔丁基抗-（2S，3S，αS）-2-羟基-3-N-苄基-N-α-甲基苄基氨基丁酸酯选择性地转化为叔丁基抗-（2S，3S，αS）-2-叠氮基-3-N-苄基-N-α-甲基苄基氨基丁酸通过叠氮鎓离子的形成和与叠氮化物的区域选择性打开。（2S，3S，alphaS）-2-叠氮基-3-氨基丁酸叔丁酯通过

  DOI：

  10.1039/b306936m
• 作为产物：
  描述：

  tert-butyl (3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)butanoate 在 (1S)-(+)-10-樟脑磺哑嗪 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 19.0h， 生成 tert-butyl (2S,3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)-2-hydroxybutanoate
  参考文献：
  名称：

  Nine Enzymes Are Required for Assembly of the Pacidamycin Group of Peptidyl Nucleoside Antibiotics

  摘要：

  Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a beta-peptide and a ureido linkage as well as a 3'-deoxyuridine nucleoside attached to DABA(3) of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.

  DOI：

  10.1021/ja2011109

文献信息

• Asymmetric synthesis of vicinal amino alcohols: xestoaminol C, sphinganine and sphingosine
  作者：Elin Abraham、Stephen G. Davies、Nicholas L. Millican、Rebecca L. Nicholson、Paul M. Roberts、Andrew D. Smith

  DOI：10.1039/b801357h

  日期：——

  beta-unsaturated esters, via conjugate addition of lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide and subsequent in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine, has been used as the key step in the asymmetric synthesis of N,O-diacetyl xestoaminol C (41% yield over 8 steps), N,O,O-triacetyl sphinganine (30% yield over 8 steps) and N,O,O-triacetyl sphingosine (30% yield over 7 steps)

  通过共轭添加（S）-N-苄基-N-（α-甲基苄基）酰胺锂并随后用（+）-（樟脑磺酰基）氧杂氮丙啶原位烯醇氧化，对α，β-不饱和酯进行高度非对映选择性的抗氨基羟化反应用作非对称合成N，O-二乙酰基异丁烯醇C（8步中产率为41％），N，O，O-三乙酰基鞘氨醇（8步中产率为30％）和N，O的关键步骤O-三乙酰基鞘氨醇（7步收率30％）。
• Microconine [N-methyl-2-methyl-3-methoxy-6-(deca-l’,3′,5′-trienyl)piperidine, an alkaloid from Microcos paniculata]: Synthesis, stereochemistry and spectroscopic data
  作者：Stephen G. Davies、Ai M. Fletcher、Paul M. Roberts、Cameron E. Taylor、James E. Thomson

  DOI：10.1016/j.tet.2020.131860

  日期：2021.1

  5′-trienyl)piperidine], an alkaloid found in Microcos paniculata, are reported. The asymmetric synthesis of the (2S,3R,6S)- and (2S,3S,6S)-stereoisomeric forms [epimeric at C(3)] of this compound allows the unambiguous assignment of the relative 2,3-cis-3,6-cis-configuration of the natural product. The synthesis uses the conjugate addition of enantiopure lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to

  明确分离的Microconine原始样品[ N-甲基-2-甲基-3-甲氧基-6-（deca-1'，3'，5'-三烯基）哌啶]的明确1 H NMR数据，Microcos中发现的一种生物碱paniculata，据报道。该化合物的（2 S，3 R，6 S）-和（2 S，3 S，6 S）-立体异构体形式的不对称合成[在C（3）上的异构体]允许相对相对的2，天然产物的3-顺-3,6-顺-构型。合成使用对映体纯锂（S）-N-苄基-的共轭加成N-（α-甲基苄基）酰胺至巴豆酸叔丁酯，并随后与（+）-樟脑磺酰基恶二丙啶进行烯醇氧化，以生成在目标物中发现的必需C（2）和C（3）立体中心。详细阐述后，使用分子内还原胺化作用形成哌啶环，并伴随形成C（6）立体异构中心。特定旋转数据的比较与具有绝对（2 R，3 R，6 R）-构型的生物碱一致。
• Microcosamine A, Microgrewiapine A and Microgrewiapine B: three homochiral alkaloids?
  作者：Stephen G. Davies、Ai M. Fletcher、Paul M. Roberts、Cameron E. Taylor、James E. Thomson

  DOI：10.1016/j.tet.2021.132056

  日期：2021.6

  nOe analyses allow unambiguous assignment of relative configuration of the alkaloids. Comparison of specific rotation data for microcosamine A and microgrewiapine B is consistent with both possessing the absolute (2S,3R,6S)-configuration. For microgrewiapine A, conflicting data regarding the absolute configuration are revealed: in the isolation study a Mosher’s analysis concludes a (2S,3R,6S)-configuration

  报道了microcosamine A、microgrewiapine A 和 microgrewiapine B（Microcos paniculata生物碱）的不对称合成。将锂 ( S ) -N-苄基-N- (α-甲基苄基)酰胺与巴豆酸叔丁酯共轭加成，然后烯醇氧化生成靶标的 C(2) 和 C(3) 立体中心，随后非对映选择性分子内还原胺化用于形成哌啶环，同时产生 C(6) 立体中心。1 H NMR 3 J耦合常数和 nOe 分析允许明确分配生物碱的相对构型。microcosamine A 和 microgrewiapine B 的比旋光度数据的比较与两者都具有绝对 (2 S ,3 R ,6 S )-构型一致。对于 microgrewiapine A，揭示了关于绝对构型的相互矛盾的数据：在隔离研究中，Mosher 的分析得出 (2 S ,3 R ,6 S )-构型的结论，但比旋光度数据的比较表明
• Asymmetric synthesis of N,O-diacetyl-3-epi-xestoaminol C: structure and absolute configuration confirmation of 3-epi-xestoaminol C
  作者：Susanna G. Archer、Kristína Csatayová、Stephen G. Davies、Ai M. Fletcher、Paul M. Roberts、James E. Thomson

  DOI：10.1016/j.tetlet.2016.02.021

  日期：2016.3

  The asymmetric synthesis of N,O-diacetyl-3-epi-xestoaminol C is reported. The synthesis employs diastereoselective aminohydroxylation of tert-butyl crotonate [conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide, then in situ enolate oxidation with (+)-camphorsulfonyloxaziridine (CSO)] and a diastereoselective reduction protocol as the key stereodefining steps. The synthetic sample of

  报道了N，O-二乙酰基-3-表位-异羟氨基C的不对称合成。该合成采用巴豆酸叔丁酯的非对映选择性氨基羟基化[共价添加锂（S）-N-苄基-N-（α-甲基苄基）酰胺，然后用（+）-樟脑磺酰基磺酰氧氮丙啶（CSO）原位烯醇氧化]和非对映选择性还原协议是确定立体声的关键步骤。为了便于纯化，分离了天然产物的合成样品，为其N，O-二乙酰基衍生物。在从可商购的10个步骤和17％的总产率制备这种材料叔巴豆酸丁酯。该合成明确地确认了天然产物的分配结构和绝对（S，S）构型。
• Nine Enzymes Are Required for Assembly of the Pacidamycin Group of Peptidyl Nucleoside Antibiotics
  作者：Wenjun Zhang、Ioanna Ntai、Megan L. Bolla、Steven J. Malcolmson、Daniel Kahne、Neil L. Kelleher、Christopher T. Walsh

  DOI：10.1021/ja2011109

  日期：2011.4.13

  Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a beta-peptide and a ureido linkage as well as a 3'-deoxyuridine nucleoside attached to DABA(3) of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.