25580-38-5Relevant articles and documents
Biocatalytic access to α,α-dialkyl-α-amino acids by a mechanism-based approach
Fesko, Kateryna,Uhl, Michael,Steinreiber, Johannes,Gruber, Karl,Griengl, Herfried
supporting information; experimental part, p. 121 - 124 (2010/04/04)
(figure presented) New donors - new products: Threonine aldolases (L-TA, D-TA) have now been found to accept donors other than glycine. In a simple asymmetric biocatalytic aldol reaction alanine, serine, and cysteine reacted with a range of simple acceptor aldehydes to yielded α-substituted serine derivatives (see scheme; PLP=pyridoxal phosphate).
Asymmetric synthesis of all stereoisomers of a-methylthreonine using an organocatalytic steglich rearrangement reaction as a key step
Dietz, Friedrich R.,Groeger, Harald
experimental part, p. 4208 - 4218 (2011/04/12)
An efficient synthetic route to all four stereoisomers of a-methylthreonine has been established. Each type of stereoisomer has been isolated in diastereomerically pure form and with an enantiomeric excess of at least 86% ee. The key step in this multi-st
α-Alkylation versus retro-O-Michael/γ-alkylation of bicyclic N,O-acetals: an entry to α-methylthreonine
Aydillo, Carlos,Avenoza, Alberto,Busto, Jesus H.,Jimenez-Oses, Gonzalo,Peregrina, Jesus M.,Zurbano, Maria M.
experimental part, p. 2829 - 2834 (2009/06/28)
The synthesis of a new threonine equivalent based on a bicyclic N,O-acetal substructure incorporating four stereogenic centres is developed from Boc-l-threonine methyl ester in one step. Its use as an excellent chiral building block was demonstrated in a new diastereoselective synthesis of α-methylthreonine by an α-alkylation reaction and in the synthesis of chiral α,β-dehydroamino acid derivatives, using the tandem retro-O-Michael/γ-alkylation reactions as key steps.
α-Methylserinals as an access to α-methyl-β-hydroxyamino acids: Application in the synthesis of all stereoisomers of α- methylthreonine
Avenoza, Alberto,Busto, Jesus H.,Corzana, Francisco,Peregrina, Jesus M.,Sucunza, David,Zurbano, Maria M.
, p. 719 - 724 (2007/10/03)
The asymmetric synthesis of all stereoisomers of α-methylthreonine using a stereodivergent synthetic route starting from (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals is reported. The key step involves the asymmetric addition of methylmagnesium bromide to these aldehydes with a high level of asymmetric induction being observed. This methodology represents a powerful tool for the synthesis of different β-substituted α-methylserines.
Functionalised 2,3-dimethyl-3-aminotetrahydrofuran-4-one and N-(3-oxo-hexahydrocyclopenta[b]furan-3a-yl)acylamide based scaffolds: Synthesis and cysteinyl proteinase inhibition
Watts, John,Benn, Alex,Flinn, Nick,Monk, Tracy,Ramjee, Manoj,Ray, Peter,Wang, Yikang,Quibell, Martin
, p. 2903 - 2925 (2007/10/03)
A stereoselective synthesis of functionalised (2R,3R)-2,3-dimethyl-3- amidotetrahydrofuran-4-one, its (2S,3R)-epimer and (3aR,6aR)-N-(3-oxo- hexahydrocyclopenta[b]furan-3a-yl)acylamide cysteinyl proteinase inhibitors has been developed using Fmoc-protected scaffolds 6-8 in a solid-phase combinatorial strategy. Within these scaffolds, the introduction of an alkyl substituent α to the ketone affords chiral stability to an otherwise configurationally labile molecule. Preparation of scaffolds 6-8 required stereoselective syntheses of suitably protected α-diazomethylketone intermediates 9-11, derived from appropriately protected α-methylthreonines (2R,3R)-12, (2R,3S)-13 and a protected analogue of (1R,2R)-1-amino-2- hydroxycyclopentanecarboxylic acid 14. Application of standard methods for the preparation of amino acid α-diazomethylketones, through treatment of the mixed anhydride or pre-formed acyl fluorides of intermediates 12-14 with diazomethane, proved troublesome giving complex mixtures. However, the desired α-diazomethylketones were isolated and following a lithium chloride/acetic acid promoted insertion reaction provided scaffolds 6-8. Elaboration of 6-8 on the solid phase gave α,β-dimethyl monocyclic ketone based inhibitors 38a-f, 39a,b,d,e,f and bicyclic inhibitors 40a-e that exhibited low micromolar activity against a variety of cysteinyl proteinases.
Preparation of (R,R)- or (S,S)-2-Amino-3-hydroxycarboxylic Acids (allo-Threonine Analogs) by Acylation/Reduction of t-Butyl 2-t-Butyl-3-methyl-4-oxoimidazolidine-1-carboxylate (Boc-BMI)
Blank, Stefan,Seebach, Dieter
, p. 889 - 896 (2007/10/02)
While there are numerous methods of preparing threonine analogs by aldol additions of chiral glycine derivatives to aldehydes, only few general routes leading to the epimers with C,C-bond formation are presently available.This paper describes the acylation of the title compound 1 with acyl chlorides (-> trans-products 2-9), the subsequent reduction with LiBHEt3 in THF (-> hydroxyalkylated BMI derivatives 10-14), and acidic hydrolysis to the free allo-threonines 18-22.The first two steps are totally stereoselective (by NMR analysis), and the overall yields from BocBMI are in the order of 30-60percent.Only allo-threonines without branching in the γ-position are accessible by this method.In one case we have also applied this sequence of steps to prepare an α-branched allo-threonine derivative 26. - The 5-acyl-BocBMI derivatives 2-9 are remarkably stable to epimerization at the center between the two carbonyl groups.Possible reasons for this are discussed and are partially supported by an X-ray crystal structure analysis of the phenacetyl derivative 6. Key words: EPC synthesis of amino acids; non-proteinogenic amino acids; diastereoselective reduction with superhydride (LiBHEt3)
Stereoselective Alkylierung an C(α) von Serin, Gycerinsaeure, Thereonin und Weinsaeure ueber heterocyclische Enolate mit exocyclischer Doppelbindung
Seebach, Dieter,Aebi, Johannes D.,Gander-Coquoz, Marlyse,Naef, Reto
, p. 1194 - 1216 (2007/10/02)
The chiral, non-racemic title acids are converted to methyl dioxalene- (cf. 13), oxazoline- (4) and oxazolidine-carboxylates (cf. 9).Deprotonation by Li(i-Pr)2N at dry-ice temperature gives solutions of the litium enolates A-D with exocyclic enolate double bonds.These are stable enough with respect to β-elimination (Scheme 1) to be alkylated with or without cosolvents such as HMPA or DMPU.The products are formed in good to excellent yields and, with the exception of the tartrate derived acetonide (see Schemem 2), with diastereoselectivities above 90percent.While the tartrate- and threonine-derived enolates (A and B, resp.) are chiral due to the second stereogenic center of the precursors, the serine- and glyceric-acid-derived enolates are non-racemic due to a tert butyl-substituted (pivalaldehyde-derived) acetal center (C and D, resp.).The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glycerine-acid derivatives (Scheme 5) with quaternary stereogenic centers.The configurations of the products are determined by NOE-NMR measurements and by chemical correlation.These show taht the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is alredy substituted ('syn'-attack).The 'syn'-attack is postulated to arise from strong folding of the heterocyclic ring due to elelctronic repulsion between the enolate ?-system and non-bonding elelctron pairs on the heteroatoms (see Scheme 6).
