Yu. N. Belokon

General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine

Synthese en particulier de serine, hydroxy-3 valine, hydroxy-2 phenylserine, phenylserine et methylenedioxy-3,4 phenylserine

A simple stereochemical model of pyridoxal-dependent aldolase: Asymmetric conversions of the amino acid fragment in chiral complexes of potassium a and Δ bis-/n-salicylideneaminoacidato/cobaltate(III)

Abstract Several chiral Co 3+ complexes with Schiff bases of amino acids glycine ( 1 ), valine ( 3 ), threonine ( 6 ), and salicylaldehyde or 3-methylsalicylaldehyde of the same amino acids ( 2 , 4 and 5 ) have been synthesized. Diastereomers ( a and b ) of compounds 3 – 6 were separated on Al 2 O 3 and enantiomers ( a and b ) of compounds 1 and 2 were resolved with brucine and strychnine. The structures of the obtained compounds were determined by elemental analysis, UV, PMR and ORD spectra. The Δ-absolute configuration of 5a was established by X-ray structural analysis. On this basis the Δ-absolute configuration was assigned to all a isomers and the Δ-absolute configuration to all b isomers. Kinetics and stereochemistry of α-proton exchange of the amino acid fragment in 1 – 4 was studied. Exchange of both protons of the glycine fragment in 1 proceeds with approximately the same rate, while the exchange of the α-protons in 2 proceed with different rates. The k R ex /k S ex ratio was experimentally established to be approximately 10.

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using NiII complexes of their Schiffs bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of α-methyl-α-amino acids with high enatiomeric purity (ee >95%).

Anionic chiral cobalt(III) complexes as catalysts of asymmetric synthesis of cyanohydrins

Chiral coordinatively saturated cobalt(III) complexes with Schiff bases of enantio-pure amino acids are formed as Λ and Δ-isomers, which are not transformed into each other under normal conditions. These complexes catalyze the formation of enantiomerically enriched cyanohydrins from aldehydes and Me3SiCN under homo-and heterogeneous catalysis.

A new synthesis of (R)- and (S)-2-2H-amino acids, including (R)- and (S)-2-2H1-glycine via stereochemically inert Co(III) complexes

Abstract Chemical synthesis of deuterated optically active 2- 2 H-amino acids via chiral complexes [Co(3-X-Sal-(S)-2- 1 H-aa) 2 ]Na, where X is H, Me; aa is valine, norvaline, tyrosine, methionine, alanine and glycine; Sal is salicylaldehyde, is described. The technique includes preparation of a mixture of XXX and Δ diastereomeric complexes of [Co(3-X-Sal-(S)-2- 1 H-aa) 2 ]Na which are separated on Al 2 O 3 . Then under the action of NaOD in D 2 O the 2- 1 H of the amino acid moiety is exchanged by deuterium, the resulting mixture of deuterated diastereomers is again separated on Al 2 O 3 , and optically active 2- 2 H aa are isolated after electrochemical reduction of pure deuterated diasteroisomers. S and R-2- 2 H 1 glycines are obtained by stereospecific 1 H- 2 H exchange of glycine moiety in XXX and Δ [Co(3-Mesal-gly) 2 ]Na.

Asymmetric synthesis and retroracemisation of amino acids via copper(II) complexes with schiff bases between chiral 1-(N,N-dimethylaminomethyl)-2-formylcymantrene and dipeptides

Abstract 1-(N,N-Dimethylaminomethyl)-2-formylcymantrene (AFCMT) has been resolved into enantiomers through an intermediate formation of diastereomeric complexes with ( S )-Ala-( S )-Ala, ( S )-Ala-Gly and Gly-( S )-Ala. By the X-ray anomalous dispersion method the absolute configuration of its enantiomers has been determined: (-) 436 AFCMT-( S ), (+) 436 AFCMT-( R ). Alkylation of enantiomeric complexes ( R )-and ( S )-AFCMT-(GlyGly) Cu(II) with acetaldehyde gives, respectively, ( R )-and ( S )-Thr with an asymmetric yield of 92–98% and ( R )- and ( S )-allo-Thr with an asymmetric yield of 95–100%, only the N-terminal glycine being alkylated. The AFCMT enantiomers were also employed for retroracemisation of ( R,S )-Ala-( R,S )-Nva; in this case an excess of ( S )-Ala and ( R )-Nva is obtained for ( S )-AFCMT. ( R )- and ( S )-AFCMT are not liable to racemisation in the course of the threonine synthesis and retroracemisation of depeptides and can be repeatedly employed for these transformations.

Asymmetric synthesis of 6-18F-L-FDOPA using chiral Nickel(II) complexes

A new procedure was suggested for asymmetric synthesis of of 6-[18F]fluoro-3,4-L-dihydroxyphenylalanine (6-18F-L-FDOPA), an important radiotracer for studies of the dopaminergic system by positron emission tomography (PET). The key step of the synthesis is stochiometric asymmetric alkylation of chiral Ni(II) complexes using 3,4-methylenedioxy-6-[18F]fluorobenzyl bromide as alkylating agent. A series of Ni(II) complexes containing various substituents in the benzyl group were tested. The highest enantiomeric purity of 6-18F-L-FDOPA was attained with the complex derived from (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide, Ni-DCBPB-Gly, under mild alkylation conditions (CH2Cl2, 40°C, potassium tert-butylate as base). Such conditions are favorable from the viewpoint of synthesis automation. The radiochemical yield of 6-18F-L-FDOPA corrected for the radioactive decay was 10–15% at a synthesis time of 120 min, including purification by semipreparative HPLC. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was as high as 95%, meeting the requirements for using 6-18F-L-FDOPA in PET practice.

Asymmetric addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines

The asymmetric Michael addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines was carried out. The maximum chemical yield of diastereomeric products amounted to 95 %. The best asymmetric induction (42 % e.e.) was achieved in the case of catalysis by (S)-prolinol. The diastereomeric mixture was converted to a mixture of stereoisomeric 3-methyl-2-methoxycarbonylpyrrolidines. Absolute configurations of (2S,3S)-and (2R,3S)-isomers formed in excess were determined using GLC by comparison with authentic samples of racemic and optically pure forms of 3-methylproline.

Asymmetric trimethylsilylcyanation of aldehydes catalyzed by chiral salen TiIV complexes with theC 1 symmetry

Asymmetric trimethylsilylcyanation of a number of aromatic and aliphatic aldehydes catalyzed by chiral TiIV complexes preparedin situ from Ti(OPri)4 and (1S)-[N,N′-bis(2′-hydroxy-3′-tert-butylbenzylidene)]-1,2-diaminoalkanes gives products with (S)-absolute configurations.

Asymmetric alkylation catalyzed by chiral alkali metal alkoxides of TADDOL. Synthesis of α-methyl amino acids

It is shown that sodium alkoxides formed from (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-bis(diphenylmethanol) ((R,R)-TADDOL) and some of its derivatives can be used as chiral catalysts for enantioselective alkylation of Schiffs bases derived from alanine with reactive alkyl halides. Acid hydrolysis of the reaction products affords (R)-α-methylphenyl-alanine, (R)-α-allylalanine, and (R)-α-methylnaphthylalanine in 61–93% yields and withee 69–94%. When (S,S)-TADDOL is used, the (S)-amino acid is formed. A mechanism explaning the observed features of the reaction is proposed.