- Development of a triazinedione-based dehydrative condensing reagent containing 4-(dimethylamino)pyridine as an acyl transfer catalyst
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A new triazinedione-based reagent, (N,N′-dialkyl)triazinedione-4-(dimethylamino)pyridine (ATD-DMAP) was developed for the operationally simple dehydrative condensation of carboxylic acids. This reagent comprises an ATD core and DMAP as the leaving group, which is liberated into the reaction system to accelerate acyl transfer reactions. Upon adding ATD-DMAP to a mixture of carboxylic acids and alcohols in the presence of an amine base, the corresponding esters were formed rapidly at room temperature. Moreover, dehydrative condensation between carboxylic acids and amines using ATD-DMAP proceeded in high yield.
- Liu, Jie,Fujita, Hikaru,Kitamura, Masanori,Shimada, Daichi,Kunishima, Munetaka
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supporting information
p. 4712 - 4719
(2021/06/11)
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- Development of triazine-based esterifying reagents containing pyridines as a nucleophilic catalyst
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We have developed new triazine-based esterifying reagents comprising pyridines that can act as a nucleophilic catalyst. 1-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-3,5-lutidinium chloride (DMT-3,5-LUT) was found to exhibit a superior reactivity for the dehydrating condensation reaction between carboxylic acids and alcohols. The reaction of DMT-3,5-LUT with carboxylic acids produces intermediacy of acyloxytriazines, which is known to exhibit moderate reactivity toward alcohols, with concomitant liberation of 3,5-lutidine. The subsequent chemical transformation of the acyloxytriazines and alcohols into esters can be accelerated by the action of 3,5-lutidine as a nucleophilic catalyst. The detailed reaction mechanism revealed by a time-course analysis of the reactions is also discussed.
- Yamada, Kohei,Liu, Jie,Kunishima, Munetaka
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supporting information
p. 6569 - 6575
(2018/09/25)
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- A practical aryl unit for azlactone dynamic kinetic resolution: Orthogonally protected products and a ligation-inspired coupling process
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The first strategy for bringing about enantioselective azlactone dynamic kinetic resolution to generate orthogonally protected amino acids has been developed. In the presence of a C2-symmetric squaramide-based catalyst, benzyl alcohol reacts with novel yet readily prepared tetrachloroisopropoxycarbonyl-substituted azlactones to generate trapped phthalimide products of significant synthetic interest with excellent enantiocontrol. These materials are masked amino acids which are demonstrably orthogonally protected: cleavage of the phthalimide can be achieved in the presence of the ester and vice versa. This process could be utilized to bring about a highly stereoselective ligation-type coupling of protected serines (at stoichiometric loadings) with racemic azlactones derived from both natural and abiotic amino acids. After deprotection, a subsequent base-mediated Oa??N acyl transfer occurs to form a dipeptide.
- Tallon, Sean,Manoni, Francesco,Connon, Stephen J.
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p. 813 - 817
(2015/02/19)
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- Solventless mechanosynthesis of N-protected amino esters
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Mechanochemical derivatizations of N- or C-protected amino acids were performed in a ball mill under solvent-free conditions. A vibrational ball mill was used for the preparation of N-protected α- and β-amino esters starting from the corresponding N-unmasked precursors via a carbamoylation reaction in the presence of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to be more suitable for the synthesis of amino esters from N-protected amino acids via a one-pot activation/esterification reaction in the presence of various dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were straightforward, leading to the final products in reduced reaction times with improved yields and simplified work-up procedures.
- Konnert, Laure,Lamaty, Frederic,Martinez, Jean,Colacino, Evelina
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p. 4008 - 4017
(2014/05/20)
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- Fully enzymatic N→C-directed peptide synthesis using C-terminal peptide α-carboxamide to ester interconversion
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Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides with some important advantages. For instance, stoichiometric amounts of expensive coupling reagents are not required and racemisation does not occur rendering purification easier compared to chemical peptide synthesis. In this paper, a novel interconversion reaction of peptide C-terminal α-carboxamides into primary alkyl esters with alcalase was used to develop a fully enzymatic peptide synthesis strategy. For each elongation step a cost-efficient amino acid carboxamide building block was used followed by the interconversion of the elongated peptide carboxamide to the corresponding primary alkyl ester. These peptide esters are the starting materials for the next enzymatic peptide elongation step. Copyright
- Nuijens, Timo,Piva, Elena,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
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experimental part
p. 1039 - 1044
(2011/07/09)
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- Fully enzymatic peptide synthesis using C-terminal tert-butyl ester interconversion
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Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides with some important advantages. For instance, stoichiometric amounts of expensive coupling reagents are not required an
- Nuijens, Timo,Cusan, Claudia,Van Dooren, Theodorus J. G. M.,Moody, Harold M.,Merkx, Remco,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
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experimental part
p. 2399 - 2404
(2011/02/21)
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- Versatile selective α-carboxylic acid esterification of N-protected amino acids and peptides by alcalase
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Under continuous removal of water, the industrial protease Alcalase allows selective synthesis of α-carboxylic acid methyl, ethyl, benzyl, allyl, 2-(trimethylsilyl)ethyl, and tert-butyl esters of amino acids and peptides under mild conditions in very high
- Nuijens, Timo,Cusan, Claudia,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
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scheme or table
p. 809 - 814
(2009/07/11)
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- Enzymatic synthesis of C-terminal arylamides of amino acids and peptides
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(Chemical Equation Presented) A mild and cost-efficient chemo-enzymatic method for the synthesis of C-terminal arylamides of amino acid and peptides is described. Using the industrial serine protease Alcalase under near-anhydrous conditions, C-terminal arylamides of N-Cbz-protected amino acids and peptides could be obtained from the corresponding C-terminal carboxylic acids, methyl (Me) or benzyl (Bn) esters, in high chemical and enantio- and diastereomeric purities. Yields ranged between 50% and 95% depending on the size of the aryl substituents and the presence of electron-withdrawing substituents. Complete α-C-terminal selectivity could be obtained even in the presence of various unprotected side-chain functionalities such as β/γ-carboxyl, hydroxyl, and guanidino groups. In addition, the use of the cysteine protease papain and the lipase Cal-B gave anilides in high yields. The chemo-enzymatic synthesis of arylamides proved to be completely free of racemization, in contrast to the state-of-the-art chemical methods.
- Nuijens, Timo,Cusan, Claudia,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
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supporting information; experimental part
p. 5145 - 5150
(2009/12/06)
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- A novel 1-tert-butoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI)-catalyzed esterification of N-protected amino acids with nearly equimolar amounts of alcohols in the presence of Boc2O
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A very mild, BBDI-catalyzed esterification using approximately equimolar amounts of N-protected amino acids and alcohols, in junction with Boc2O is described.
- Saito, Yukako,Watanabe, Tomokazu,Takahata, Hiroki
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p. 3099 - 3102
(2007/10/03)
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- Simple and mild esterification of N-protected amino acids with nearly equimolar amounts of alcohols using 1-tert-butoxy-2-tert-butoxycarbonyl-1,2- dihydroisoquinoline
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A very mild, one-step esterification using nearly equimolar amounts of N-protected amino acids and alcohols, in conjunction with 1-tert-butoxy-2-tert- butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) as a novel condensing reagent is described.
- Saito, Yukako,Yamaki, Toru,Kohashi, Fumiaki,Watanabe, Tomokazu,Ouchi, Hidekazu,Takahata, Hiroki
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p. 1277 - 1279
(2007/10/03)
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- Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAI
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Novel solution and solid-phase methods for the synthesis of carbonates and carbamates were developed using cesium bases and TBAI via a three-component coupling. Cesium carbonate not only promoted successful carbonylations of alcohols and carbamations of amines, but also suppressed common side reactions traditionally seen using existing protocols. Various alcohols and amines were examined, using a wide array of alkyl halides, and the results demonstrated this methodology was highly chemoselective. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the corresponding products exclusively, offering a wide variety of applications such as novel protecting groups and peptidomimetic syntheses.
- Salvatore, Ralph N,Chu, Feixia,Nagle, Advait S,Kapxhiu, Elona A,Cross, Richard M,Jung, Kyung Woon
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p. 3329 - 3347
(2007/10/03)
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- Papain catalysed Esterification of N-Protected Amino Acids
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N-Protected amino acids and amino diacids were converted to their corresponding esters catalysed by immobilized papain with a high concentration of alcohols under mild conditions in a two-phase system.
- Chen, Shui-Tein,Wang, Kung Tsung
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p. 327 - 328
(2007/10/02)
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