Asymmetric Synthesis of Phosphorus Analogs of Amino Acids

Kukhar, V. P.; Soloshonok, Vadim A.; Solodenko, V. A.

doi:10.1080/10426509408021478

Cited by 124 publications

(30 citation statements)

References 46 publications

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“…These phosphoramidates were metalated by using sBuLi/N,N,N',N'-tetramethylethylenediamine (TMEDA) to give a-aminobenzyllithiums that isomerised to aaminophosphonates in yields of up to 80 % with retention of the configuration at the carbon atom. The intermediate tertiary organolithiums were found to be microscopically configurationally stable from À78 to 0 8C in Et 2 O. The protected a-aminophosphonates were deblocked by using boiling 6 m HCl or preferably…”

Section: Introductionmentioning

confidence: 99%

“…[1] Therefore, racemic and preferably chiral, non-racemic a-aminophosphonic acids and peptides containing them have been synthesised to address various biological effects. [2] N-Benzyl a-aminobenzylphosphonic acids were found to be potent inhibitors of human prostatic acid phosphatase. [3] (R)-Phosphatyrosine (the phosphonic acid analogue of l-tyrosine) is a component of naturally occurring hypotensive tripeptides.…”

Section: Introductionmentioning

confidence: 99%

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Preparation of α‐Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α‐Aminobenzyllithiums

Kuliszewska

Hanbauer

Hammerschmidt

2008

Chemistry A European J

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The enantiomers of 1-phenylethylamine were phosphorylated with diethyl chlorophosphate/Et(3)N and then Boc-protected (Boc=tert-butoxycarbonyl) at the nitrogen atom. These phosphoramidates were metalated by using sBuLi/N,N,N',N'-tetramethylethylenediamine (TMEDA) to give alpha-aminobenzyllithiums that isomerised to alpha-aminophosphonates in yields of up to 80 % with retention of the configuration at the carbon atom. The intermediate tertiary organolithiums were found to be microscopically configurationally stable from -78 to 0 degrees C in Et(2)O. The protected alpha-aminophosphonates were deblocked by using boiling 6 M HCl or preferably Me(3)SiBr/(allyl)SiMe(3). When the Boc group was replaced by the diethoxyphosphinyl group, the alpha-aminobenzyllithium intermediate partially enantiomerised even at -78 degrees C and rearranged to yield an alpha-aminophosphonate with 50 % ee (ee=enantiomeric excess). Similarly, N-Boc-protected phosphoramidates derived from racemates and/or enantiomers of 1-(1-naphthyl)ethyl-, 1-indanyl- and 1,2,3,4-tetrahydro-1-naphthylamine or 1-azidoindan- and 1-azido-1,2,3,4-tetrahydronaphthalene were converted to aminophosphonates in good yields. Deblocking gave alpha-aminophosphonic acids of excellent enantiomeric excess (97-99 %), as determined by means of HPLC on a chiral ion-exchange stationary phase based on quinine carbamate. When racemic Boc-protected diethyl phosphoramidate derived from 1,2,3,4-tetrahydro-1-naphthylamine was metalated with LiTMP/TMEDA (TMP=2,2,6,6-tetramethylpiperidine), 1-hydroxyethylphosphonamidates resulted. The configuration of the main isomer was determined by means of a single-crystal X-ray structure analysis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation of α‐Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α‐Aminobenzyllithiums

Kuliszewska

Hanbauer

Hammerschmidt

2008

Chemistry A European J

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“…Development of the synthesis of optically active ␣-hydroxyand ␣-aminophosphonic acids has begun only recently (2,15). ʈ Processes applying the catalytic amounts of the source of chirality are especially attractive.…”

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confidence: 99%

Asymmetric hydrogenation of α,β-unsaturated phosphonates with Rh-BisP* and Rh-MiniPHOS catalysts: Scope and mechanism of the reaction

Gridnev

Yasutake

Imamoto

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Optically active 1,2-bis(alkylmethylphosphino)ethanes and bis(alkylmethylphosphino)methanes are unique diphosphine ligands combining the simple molecular structure and P-stereogenic asymmetric environment. This work shows that these ligands exhibit excellent enantioselectivity in rhodium-catalyzed asymmetric hydrogenation of ␣,␤-unsaturated phosphonic acid derivatives. The enantioselective hydrogenation mechanism elucidated by NMR study is also described. The ␣-hydroxy-and ␣-aminophosphonic acids have an extremely rich and varied spectrum of biological activity (1, 2) that is stipulated by their ability to act as antagonists for amino acids inhibiting enzymes involved in the amino acids' metabolism. They can be used as herbicides (3, 4), antiviral drugs (5), antibiotics (6), and neurodrugs (7). Being able to affect the biological activity of cells (8), some of them can inhibit HIV protease (9) and alanine racemase (alafosfalin) (10). Peptide ␣-hydroxyphosphonates are known to be rennin inhibitors (11).The biological activity of the phosphonic acids highly depends on the absolute configuration of its ␣-chiral center. An excellent example is alafosfalin, [N-(L-alanyl)-L-1-aminoethyl]phosphonic acid (S,R)-diastereomer. Only this diastereomer unlike (R,R)-, (S,S)-, and (R,S)-diastereomers shows high antibacterial activity (12, 13).Development of the synthesis of optically active ␣-hydroxyand ␣-aminophosphonic acids has begun only recently (2, 15). ʈ Processes applying the catalytic amounts of the source of chirality are especially attractive. Thus, hydrophosphonylation of imines catalyzed by heterobimetallic complexes Ln-K-BINOL (16) and hydrophosphonylation of aldehydes catalyzed by analogous complexes Al-Li-BINOL (17) give the ␣-amino-and ␣-hydroxyphosphonic acids, respectively, with high enantiomeric excesses (ee's). Furthermore, the catalytic asymmetric Michael addition to ␣,␤-unsaturated phosphonates (18, 19) and the allylation reaction of ␣-acetylamino-␤-ketophosphonates (20) have been successfully used for the synthesis of phosphonic acid derivatives with the stereogenic centers in the ␣-or ␤-position.Another convenient approach to the synthesis of the acids is the asymmetric hydrogenation of the corresponding unsaturated precursors. By this means, the phosphorus analogs of ␣-aminoor ␣-hydroxycarboxylic acids were obtained with up to 96% ee by using the Rh complexes of chiral phosphine ligands such as (Ϫ)-BPPM (2S,4S) (21) and DuPHOS (22). Noyori and coworkers reported that ␣-substituted ␤-ketophosphonates were subjected to enantio-and diastereoselective hydrogenation by the use of the BINAP-Ru(II) complex to give the corresponding ␤-hydroxyphosphonates with exceedingly high ee's (94-98%) (23,24). Also worth mentioning is that optically active ␣-arylsubstituted ethylphosphonates, phosphorus analogs of 2-arylpropionic acids, were produced by Ir-and Ru-catalyzed asymmetric hydrogenation of ethenylphosphonates (25,26).On the other hand, we previously designed and synthesized new bidentate phosphine ligands, (S,S...

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“…This led to the stereoselective synthesis of 6-aryl-3,3a,4,5,6-pentahydrocyclopent[C]isoxazole-5-ylphosphonates [63]. The spatial structures of the products were unambiguously characterized by 1 H, 13 C, and 31 P NMR, NOESY, and 1 H-13 C COSY spectra. The hydrogen at C-3a is trans to both the phosphonate group at C-5 and the aryl group at C-6.…”

Section: Phosphorylated 45-dihydroisoxazolesmentioning

confidence: 99%

“…Since the biological activities of 1-aminophosphonic acids are largely dependent on their absolute configurations, the asymmetric synthesis of these compounds has aroused the interest of organic chemists [13]. The nucleophilic addition of a dialkyl phosphite to chiral imines or oxoiminium derivatives have constituted the majority of asymmetric syntheses of 1-aminophosphonic acids to date, although several additional interesting synthetic methods have been developed [14][15][16].…”

Section: -Aminophosphonic Acidsmentioning

confidence: 99%