Solventless Mechanosynthesis of N-Protected Amino Esters

Konnert, Laure; Lamaty, Frédéric; Martinez, Jean; Colacino, Evelina

doi:10.1021/jo500463y

Cited by 29 publications

(31 citation statements)

References 70 publications

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“…36 However, very low conversions were obtained for the N-carbamoylation reaction in the vibrational ball-mill from amino acids (instead of planetary milling, Scheme 6.8), or in the planetary ball-mill from amino esters (instead of vibrational apparatus, Scheme 6.9), probably because of the different stress phenomena (horizontally vibrating or circularly shaking milling) and quantity of energy delivered to the sample, working at 30 Hz or at 450 rpm (which corresponded to 7.5 Hz), showing that the two apparatus were not necessarily interconvertible when performing the same reaction. The same trend was observed during the solvent-less esterification of the C-terminal position of amino acids, 35 which is effective in the planetary and not in the vibrational ball-mill apparatus (Scheme 6.10).…”

Section: Synthesis Of Protected Amino Acidssupporting

confidence: 52%

“…In a similar approach, a vibrational ball-mill was used for the carbamoylation reaction of a-, b-or quaternary amino esters (Scheme 6.9), 35 sharing the same advantages as previously illustrated for the N-protection of amino acid derivatives in the planetary ball-mill 31 (Scheme 6.8) in terms of: (i) ease of recovery of pure final products, (ii) entity and nature of waste, and (iii) full conversion and yield. In addition, Z-OSu and Fmoc-OSu could be replaced by the more convenient chloride derivatives.…”

Section: Synthesis Of Protected Amino Acidsmentioning

confidence: 99%

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CHAPTER 6. Amino Acids and Peptides in Ball Milling

Métro¹,

Colacino²,

Martínez³

et al. 2014

Green Chemistry Series

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Section: Synthesis Of Protected Amino Acidssupporting

confidence: 52%

Section: Synthesis Of Protected Amino Acidsmentioning

confidence: 99%

CHAPTER 6. Amino Acids and Peptides in Ball Milling

Métro¹,

Colacino²,

Martínez³

et al. 2014

Green Chemistry Series

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“…For manganese(IV) oxide, Wako manganese(IV) oxide, powder (order number 138-09675) was used. The substrates 1p, 35) r 36) and catalyst 3 34) were prepared according to the literature procedure.…”

Section: Methodsmentioning

confidence: 99%

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

Inokuma

Jichu

Nishida

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of α-imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avoided. Furthermore, using this methodology we synthesized novel α-imino carboxylic acid derivatives such as α-imino phenyl ester, perfluoroalkyl etsers, imides, and thioester. The asymmetric Mannich reaction of those novel imine derivatives with 1,3-dicarbonyl compound is also described, and the novel α-imino imide gave improved chemical yield and stereoselectivity compared with those obtained by the use of the conventional α-imino ester-type substrate.Key words α-imino carboxylic acid derivative; heterogeneous oxidant; asymmetric organocatalysis; thiourea; unnatural α-amino acid Unnatural α-amino acids are often seen in varieties of biologically active compounds, 1-4) including pharmaceutics, and have been used as indispensable chiral building blocks for the synthesis of such active compounds.5,6) Additionally, increasing utilities of unnatural amino acids as a key structural element have also been shown in fields of chemical biology and asymmetric transformation.7-11) These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit.12,13) Enabling easy access to diverse α-amino acids only by changing nucleophiles employed, Mannich-type reaction of α-imino ester has been widely utilized for the asymmetric synthesis.14-20) Generally, condensation of glyoxalates and primary amines affords α-imino esters as the requisite substrate for Mannich-type reaction (Chart 1a); however, the glyoxalates are unstable, and suffer easy hydrolysis or polymerization at room temperature. Additionally, high susceptibility of the resulting α-imino ester to silica gel has forced us to directly use the imino esters for the Mannich reaction without purification, thereby leading to difficulty in maintaining the reaction outcome. In this context, cross-dehydrogenative coupling (CDC) has been investigated for the synthesis of α-functionalized amino acids 21-23) (Chart 1b). The CDC protocol features oxidative preparation of α-imino ester from glycinates with the use of the oxidants such as 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), CuOAc, Ru(bpy) 3 Cl 2 / light (or N-oxyl radical), or Cu(I)/molecular oxygen, followed by in situ Mannich reaction. Although the CDC protocol is free from the use of unstable glyoxalates, the in situ Mannich reaction has to be performed in the presence of the employed oxidant due to difficulty in achieving complete separation of the imino ester and oxidant, by which the use of the CDC remains within application to the coupling of oxidant-tolerant functional units. Here, we envisioned that the heterogeneous oxidation system enabling facile removal of insoluble oxidants by filtration allowed the imino ester to be readily obtained and subsequently subjected to Mannich reaction under oxidant-free conditions (Chart 1c).

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“…For example, l-proline (15; Figure2)p roved highly stable during the solvent-freem echanochemical asymmetric aldol reaction between ketonesand aldehydes. [25] In 2017, ud and Margetić reported a solvent-free deprotection of N-Boc amino acids by using p-toluenesulfonic acid under ball-milling conditions, [26] therebyb roadeningt he protection/deprotection chemistry of amino acids by mechanochemistry ( Figure 2). [ More recently,C olacino and co-workers demonstrated the compatibilityo fa mino acids and ballmilling technology after performing systematic studies on the structural modification of amino acids.…”

Section: Use and Modification Of Amino Acids In Ball Millsmentioning

confidence: 99%

From Synthesis of Amino Acids and Peptides to Enzymatic Catalysis: A Bottom‐Up Approach in Mechanochemistry

2018

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Recently, chemical reactions induced or facilitated by mechanical energy have gained recognition in diverse areas of chemical synthesis. In particular, mechanosyntheses of amino acids and short peptides, along with their applications in catalysis, have revealed the high degree of stability of peptide bonds in environments of harsh mechanical stress. These observations quickly led to the recent interest in developing mechanochemical enzymatic reactions. Experimentally, manual grinding, ball-milling techniques, and twin-screw extrusion technology have proven valuable to convey mechanical forces into a chemical synthesis. These practices have enabled the establishment of more sustainable alternatives for chemical synthesis by reducing the use of organic solvents and waste production, thereby having a direct impact on the E-factor of the chemical process. In this Minireview, the series of events that allowed the development of mechanochemical enzymatic reactions are described from a bottom-up perspective.

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Solventless Mechanosynthesis of N-Protected Amino Esters

Cited by 29 publications

References 70 publications

CHAPTER 6. Amino Acids and Peptides in Ball Milling

CHAPTER 6. Amino Acids and Peptides in Ball Milling

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

From Synthesis of Amino Acids and Peptides to Enzymatic Catalysis: A Bottom‐Up Approach in Mechanochemistry

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