37553-64-3Relevant academic research and scientific papers
Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
supporting information, p. 4267 - 4271 (2018/11/03)
A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.
Toward the synthesis and improved biopotential of an n-methylated analog of a proline-rich cyclic tetrapeptide from marine bacteria
Dahiya, Rajiv,Kumar, Suresh,Khokra, Sukhbir Lal,Gupta, Sheeba Varghese,Sutariya, Vijaykumar B.,Bhatia, Deepak,Sharma, Ajay,Singh, Shamjeet,Maharaj, Sandeep
, (2018/09/10)
An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-L-prolyl-L-N-methylleucine-OH and L-prolyl-L-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N0-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy),1H NMR (Nuclear magnetic resonance spectroscopy),13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.
Ring-closing metathesis based total synthesis of ciliatamides A and B and their structural confirmation
Avula, Krishnakumari,Mohapatra, Debendra K.
supporting information, p. 1715 - 1717 (2016/04/04)
Protecting group dependant ring-closing metathesis based approach to the total synthesis of the revised structures of ciliatamides A and B has been described. The current synthetic strategy utilizes the amino acid as starting material to introduce both the stereogenic centers. However, usage of non-racemizing reagents (EDC·HCl, HATU/NMM); for amide coupling and Grubbs' second generation catalyst for caprolactam ring synthesis makes the present approach more convenient to get the correct conclusion on absolute stereochemistry. Thus, on the basis of similar optical rotation values with the Lindsley's reported data, this synthesis further supported for the actual stereochemistry of both ciliatamides A and B is (R,R).
Synthesis of N-methyl L-phenylalanine for total synthesis of pepticinnamin e
Sun, Dequn,Zhang, Lingzi,Wang, Jin
experimental part, p. 319 - 322 (2012/09/07)
The target compounds 3, 10 and 11 were synthesized through different N-methylation strategies. The concise and efficient preparation of them in large scale was developed and 3, 10 and 11 were obtained in suitable form used for both nitrogen-end and oxygen-end extension in next coupling reaction in peptides synthesis, specifically in total synthesis of natural pepticinnamin E.
Study of intramolecular aminolysis in peptides containing N-alkylamino acids at position 2
Ryakhovsky, Vladimir V.,Ivanov, Andrey S.
supporting information; experimental part, p. 7070 - 7076 (2012/08/29)
Many peptides and proteins, containing Nα-alkylamino acids (including proline) at the second position, are prone to intramolecular aminolysis (IA) with elimination of N-terminal dipeptide sequence as 2,5-diketopiperazines (DKP). We synthesized a series of short peptides, containing N-alkylamino acids at position 2, and studied their stability in the presence of acetic acid and amines. The presence of side chains in the second and the third amino acid residues and alkylation at Nα of the third amino acid residue slowed down IA. Nα-Alkyl residue in the first amino acid residue impeded IA only in peptides, containing three or more residues. Side chains of the first amino acids did not affect significantly the cleavage rates. Acetic acid promoted IA more strongly than aqueous ammonia, while tertiary amines were less effective. Peptides with methionine-S-oxide residues were more labile than the unoxidized analogs, suggesting intramolecular assistance of the S-oxide group in aminolysis. Surprisingly, intermediate compounds of the formula Boc-Met-MeXaa-Sar-NHR underwent rapid cleavage (endopeptolysis) upon attempted acidolytic deprotection.
The first total synthesis of (-)-benzomalvin A via intramolecular Aza-Wittig reactions
Sugimori, Toshiyuki,Okawa, Tomohiro,Eguchi, Shoji,Yashima, Eiji,Okamoto, Yoshio
, p. 869 - 870 (2007/10/03)
The first total synthesis of (-)-benzomalvin A 1, which possesses quinazolin-4(3H)-one moiety and 1,4-benzodiazepin-5-one moiety, was described. Both of 6- and 7-membered ring skeletons were efficiently constructed by intramolecular aza-Wittig reactions as the key reactions.
Synthesis and conformational analysis of the multidrug resistance-reversing agent hapalosin and its non-N-methyl analog
Dinh, Tam Q.,Du, Xiaohui,Armstrong, Robert W.
, p. 6606 - 6616 (2007/10/03)
Hapalosin was initially synthesized by macrolactonization, and a second synthesis was achieved by cycloamidation. In both syntheses, three of the five stereocenters in hapalosin were established by two Brown allylboration reactions. The synthesis of the non-N-Me analog of hapalosin involved chelation-controlled reduction of a γ-amino-β-keto ester and cycloamidation. In CDCl3 at 25°C, synthetic hapalosin exists as a 2.3:1 mixture of conformers, while its non-N-Me analog exists only as a single conformer. 1H,1H-NOESY and computation reveal that the configuration of the amide bond is responsible for the conformations of the two compounds. The major conformer of hapalosin is found to be an s-cis amide, the minor conformer an s-trans amide, and the non-N-Me analog an s-trans amide. Applying distance constraints to protons that exhibit NOESY correlations, computation shows that the major conformer of hapalosin and the non-N-Me analog have very different conformations. By contrast, the minor conformer of hapalosin and the non-N-Me analog have very similar conformations.
