3059-97-0Relevant articles and documents
Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
supporting information, p. 503 - 517 (2021/03/01)
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
High-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid
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Paragraph 0056; 0058; 0066, (2018/09/13)
The invention discloses a high-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid. The high-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid is characterized by comprising the following steps: step one, reacting S-tert-butanesulfinyl amide or R-tert-butanesulfinyl amide, R-beta substituted ethyl pyruvate and tetraethyl titanate in atetrahydrofuran solvent to obtain a compound C; step two, reacting the compound C with alkyl substituted magnesium bromide under the catalyzing effect of zinc dimethyl in tetrahydrofuran to obtain acompound E; step three, reacting the compound E under the effect of ammonium chloride and anhydrous hydrogen chloride to obtain a compound F; and step four, hydrolyzing the compound F in an ethanol aqueous solution of sodium hydroxide to obtain hydrochloride of a compound G, and carrying out ion exchange to obtain the compound G. The chiral selective reaction is greatly improved, and the method issimple in process, uses cheap and easily obtained raw materials, is simple and convenient to operate, is quite suitable for industrial mass production, and has quite extensive industrial applicationprospect and market value.
A practical chemoenzymatic synthesis of (R)-isovaline based on the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide
Nojiri, Masutoshi,Yoshida, Fumi,Hirai, Yoshinori,Nishiyama, Akira,Yasohara, Yoshihiko
, p. 1 - 5 (2015/03/31)
(R)-Isovaline has potential applications in drug development, and therefore the development of an efficient method for the production of (R)-isovaline is desired. Herein we have investigated the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide into (S)-2-ethyl-2-methyl-malonamic acid, a useful synthetic intermediate in the production of (R)-isovaline, using CsAM, which is a recombinant amidase originally derived from Cupriavidus sp. KNK-J915. The produced (S)-2-ethyl-2-methyl-malonamic acid (98.6% ee) could be easily converted into (R)-isovaline by the Hofmann rearrangement. Starting from diethyl 2-methylmalonate, we obtained (R)-isovaline (99.1% ee) in 58.6% yield over eight steps, including the CsAM-catalyzed asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide.
PROCESS FOR PRODUCING SOLID AMINO ACID
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Paragraph 0076; 0077, (2014/12/09)
The problem to be solved by the present invention is to ea lily and efficiently produce an amino acid having 2 to 7 carbon atoms as a high-purity solid without complicated operation, which is useful as a synthetic intermediate for medicines or agrochemicals. The present invention is characterized in comprising a step of precipitating solid amino acid with high purity. In the present invention, the by-produced salt composed of the sulfonic acid and the amine was removed to the mother liquor by reacting an amine with a sulfonic acid salt of amino acid in an aprotic polar solvent, or by reacting a sulfonic acid with an amine salt of amino acid in an aprotic polar solvent. The sulfonic acid salt of amino acid, for example, may be produced by reacting a N-(tert-butoxycarbonyl) amino acid with a sulfonic acid, or by reacting an amino acid tert-butyl ester with a sulfonic acid.
A new type of oxidation-reduction condensation by the combined use of phenyl diphenylphosphinite and oxidant
Mukaiyama, Teruaki,Kuroda, Kiichi,Maruyama, Yuji
scheme or table, p. 63 - 82 (2010/04/23)
A new type of oxidation-reduction condensation of alcohols with sulfur, nitrogen, and oxygen nucleophiles by the combined use of phenyl diphenylphosphinite (PhOPPh2) and oxidants such as azides or diethyl azodicarboxylate (DEAD) are described. In these reactions, chiral secondary and tertiary alcohols are converted into the corresponding chiral sulfides, azides, esters and ethers under mild and neutral conditions with almost complete inversion of stereochemical configuration.
Mitsunobu approach to the synthesis of optically active α,α-disubstituted amino acids
Green, Jonathan E.,Bender, David M.,Jackson, Stona,O'donnell, Martin J.,Mccarthy, James R.
supporting information; experimental part, p. 807 - 810 (2009/08/08)
Chiral tertiary α-hydroxy esters of known stereochemical configuration were transformed to α-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the α-carbon. Several α,α- disubstituted amino acids were synthesized in high overall chemical yield and optical purity.
Chiral salen-metal complexes as novel catalysts for the asymmetric synthesis of α-amino acids under phase transfer catalysis conditions
Belokon, Yuri N,North, Michael,Churkina, Tatiana D,Ikonnikov, Nikolai S,Maleev, Victor I
, p. 2491 - 2498 (2007/10/03)
Chiral salen-metal complexes have been tested as catalysts for the C-alkylation of Schiff's bases of alanine and glycine esters with alkyl bromides under phase-transfer conditions (solid sodium hydroxide, toluene, ambient temperature, 1-10 mol% of the catalyst). The best catalyst, which was derived from a Cu(II) complex of (1R, 2R or 1S,2S)-[N,N′-bis(2′-hydroxybenzylidene)]-1,2-diaminocyclohexane, gave α-amino and α-methyl-α-amino acids with enantiomeric excesses of 70-96%.
Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions
Chinchilla, Rafael,Galindo, Nuria,Nájera, Carmen
, p. 704 - 717 (2007/10/03)
3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.
Stereocontrolled synthesis of α,α-disubstituted α-aminoaldehydes and α-aminoacids using a [3,3] allylic trichloracetimidate rearrangement
Imogai, Hassan,Petit, Yves,Larcheveque, Marc
, p. 2573 - 2576 (2007/10/03)
Sigmatropic rearrangement of trichloracetimidates derived from syn monoprotected allylic diols 3 resulting from the condensation of vinylalanes or cuprates with α-alkoxyaldehydes afforded diastereomerically pure allylic amines 6. The oxidative cleavage of these amines allowed the access to α,α-disubstituted α-aminoacids in high enantiomeric purity.
Enantioselective Synthesis of α-Branched α-Amino Acids with Bulky Substituents
Studer, Armido,Seebach, Dieter
, p. 217 - 222 (2007/10/02)
Enantiopure 5,5-disubstituted t-butyl 2-t-butyl-3-methyl-4-oxoimidazolidine-1-carboxylates readily available by diastereoselective double alkylation of the parent compound (Boc-BMI) can be converted to α-branched α-amino acids with two bulky substituents (PhCH2/Et, PhCH2/i-Pr, PhCH2/CH2C6H11) in four simple steps: hydrolysis to the amino acid amides, N-benzoylation, cleavage of the amino acid amide group, and debenzoylation (Scheme 3, products 6-10, overall yields >50percent).This procedure constitutes an extension of the scope of amino acid synthesis from (R)- and (S)-Boc-BMI. - Key Words: Amino acids, α-branched/ Highly hindered amides/ Hydrolysis of amino acid amides/ Anchimeric effect/ Phenylalanine, 2-ethyl, 2-i-propyl- and 2-cyclohexylmethyl-
