- Scalable and Selective β-Hydroxy-α-Amino Acid Synthesis Catalyzed by Promiscuous l-Threonine Transaldolase ObiH
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Enzymes from secondary metabolic pathways possess broad potential for the selective synthesis of complex bioactive molecules. However, the practical application of these enzymes for organic synthesis is dependent on the development of efficient, economical, operationally simple, and well-characterized systems for preparative scale reactions. We sought to bridge this knowledge gap for the selective biocatalytic synthesis of β-hydroxy-α-amino acids, which are important synthetic building blocks. To achieve this goal, we demonstrated the ability of ObiH, an l-threonine transaldolase, to achieve selective milligram-scale synthesis of a diverse array of non-standard amino acids (nsAAs) using a scalable whole cell platform. We show how the initial selectivity of the catalyst is high and how the diastereomeric ratio of products decreases at high conversion due to product re-entry into the catalytic cycle. ObiH-catalyzed reactions with a variety of aromatic, aliphatic and heterocyclic aldehydes selectively generated a panel of β-hydroxy-α-amino acids possessing broad functional-group diversity. Furthermore, we demonstrated that ObiH-generated β-hydroxy-α-amino acids could be modified through additional transformations to access important motifs, such as β-chloro-α-amino acids and substituted α-keto acids.
- Doyon, Tyler J.,Kumar, Prasanth,Thein, Sierra,Kim, Maeve,Stitgen, Abigail,Grieger, Abbigail M.,Madigan, Cormac,Willoughby, Patrick H.,Buller, Andrew R.
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- L -Threonine Transaldolase Activity Is Enabled by a Persistent Catalytic Intermediate
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l-Threonine transaldolases (lTTAs) are a poorly characterized class of pyridoxal-5′-phosphate (PLP) dependent enzymes responsible for the biosynthesis of diverse β-hydroxy amino acids. Here, we study the catalytic mechanism of ObiH, an lTTA essential for biosynthesis of the β-lactone natural product obafluorin. Heterologously expressed ObiH purifies as a mixture of chemical states including a catalytically inactive form of the PLP cofactor. Photoexcitation of ObiH promotes the conversion of the inactive state of the enzyme to the active form. UV-vis spectroscopic analysis reveals that ObiH catalyzes the retro-aldol cleavage of l-threonine to form a remarkably persistent glycyl quinonoid intermediate, with a half-life of a??3 h. Protonation of this intermediate is kinetically disfavored, enabling on-cycle reactivity with aldehydes to form β-hydroxy amino acids. We demonstrate the synthetic potential of ObiH via the single step synthesis of (2S,3R)-β-hydroxyleucine. To further understand the structural features underpinning this desirable reactivity, we determined the crystal structure of ObiH bound to PLP as the Schiff's base at 1.66 ? resolution. This high-resolution model revealed a unique active site configuration wherein the evolutionarily conserved Asp that traditionally H-bonds to the cofactor is swapped for a neighboring Glu. Molecular dynamics simulations combined with mutagenesis studies indicate that a structural rearrangement is associated with l-threonine entry into the catalytic cycle. Together, these data explain the basis for the unique reactivity of lTTA enzymes and provide a foundation for future engineering and mechanistic analysis.
- Kumar, Prasanth,Meza, Anthony,Ellis, Jonathan M.,Carlson, Grace A.,Bingman, Craig A.,Buller, Andrew R.
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- Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor
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The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation-elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and ?2-hydroxyleucine residues.
- Kaur, Harveen,Harris, Paul W. R.,Little, Peter J.,Brimble, Margaret A.
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supporting information
p. 492 - 495
(2015/03/05)
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- Multi-enzymatic synthesis of optically pure β-hydroxy α-amino acids
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A novel enzymatic production system of optically pure β-hydroxy α-amino acids was developed. Two enzymes were used for the system: an N-succinyl L-amino acid β-hydroxylase (SadA) belonging to the iron(II)/α-ketoglutarate-dependent dioxygenase superfamily and an N-succinyl L-amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N-succinyl aliphatic L-amino acids and produced N-succinyl β-hydroxy L-amino acids, such as N-succinyl-L-β-hydroxyvaline, N-succinyl-L-threonine, (2S,3R)-N-succinyl-L-β-hydroxyisoleucine, and N-succinyl-L-threo-β-hydroxyleucine. LasA catalyzed the desuccinylation of various N-succinyl-L-amino acids. Surprisingly, LasA is the first amide bond-forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L-leucine. By combining SadA and LasA in a preparative scale production using N-succinyl-L-leucine as substrate, 2.3 mmol of L-threo-β-hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β-hydroxy α-amino acids.
- Hibi, Makoto,Kasahara, Takuya,Kawashima, Takashi,Yajima, Hiroko,Kozono, Shoko,Smirnov, Sergey V.,Kodera, Tomohiro,Sugiyama, Masakazu,Shimizu, Sakayu,Yokozeki, Kenzo,Ogawa, Jun
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p. 767 - 774
(2015/03/18)
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- Trichormamides A and B with antiproliferative activity from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339
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Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey's method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two d-amino acid residues (d-Tyr and d-Leu) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 μM, respectively.
- Luo, Shangwen,Krunic, Aleksej,Kang, Hahk-Soo,Chen, Wei-Lun,Woodard, John L.,Fuchs, James R.,Swanson, Steven M.,Orjala, Jimmy
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p. 1871 - 1880
(2014/10/16)
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- DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
- -
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Paragraph 0384; 0385
(2013/06/06)
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- Efficient total synthesis of manzacidin B
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The highly diastereoselective synthesis of the marine natural product, (-)-manzacidin B, is described. A novel copper-catalyzed aldol reaction of the α-methylserine-derived aldehyde with an isocyanoacetate possessing (1R)-camphorsultam as the chiral auxiliary proceeded in a highly diastereoselective manner to give the (4R,5R,6R)-adduct, which was converted into manzacidin B in a few steps.
- Shinada, Tetsuro,Oe, Kentaro,Ohfune, Yasufumi
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supporting information; experimental part
p. 3250 - 3253
(2012/07/31)
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- Synthesis of γ-halogenated and long-chain β-hydroxy-α-amino acids and 2-amino-1,3-diols using threonine aldolases
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The l- and d-threonine aldolase catalyzed formation of γ-halogenated and long-chain l- and d-3-alkylserine-derivatives 1-12, respectively, was shown starting from glycine and halogenated C2- or C4-C12 aldehydes. lTA from Pseudomonas putida accepted all tested aldehydes with strongly varying diastereoselectivity (de up to 93%). Only aldehydes smaller than decanal were converted by dTA from Alcaligenes xylosoxidans with good selectivities (de up to 73%). Utilizing isobutanal enantio- and diastereopure d-syn-2-amino-3-hydroxy-4-methylpentanoic acid was obtained (ee>99%, de>95%), which was converted to the corresponding 2-amino-1,3-diol.
- Steinreiber, Johannes,Fesko, Kateryna,Mayer, Clemens,Reisinger, Christoph,Schürmann, Martin,Griengl, Herfried
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p. 8088 - 8093
(2008/02/08)
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- Total structure and inhibition of tumor cell proliferation of laxaphycins
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From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides, The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.
- Bonnard, Isabelle,Rolland, Marc,Salmon, Jean-Marie,Debiton, Eric,Barthomeuf, Chantal,Banaigs, Bernard
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p. 1266 - 1279
(2007/10/03)
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- DIRECT ORGANOCATALYTIC ASYMMETRIC REACTIONS OF ENOLIZABLE α-AMINO ALDEHYDES OR KETONES TO FORM HIGHLY ENANTIOMERICALLY ENRICHED AMINE PRODUCTS
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A method for asymmetrically forming a (diprotectedamino)-product having a chiral center and in which one enantiomer is in excess over the other is disclosed. The method comprises reacting an enolizable alpha- (diprotectedamino)-aldehyde or -ketone donor molecule with an excess of an unsaturated acceptor molecule that has one or no hydrogen atoms bonded to a carbon atom alpha to the carbon of the unsaturation. The donor and acceptor molecules are dissolved or dispersed in a liquid solvent and are in the presence of a chiral amine catalyst to form an addition product reaction medium. The reaction medium is maintained for a time sufficient to form an α-(diprotectedamino)-aldehyde or -ketone product having a chiral center formed at a carbon atom bonded to the α-(diprotectedamino) group and in which one enantiomer is in excess over the other.
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Page/Page column 42
(2010/10/20)
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- Lobocyclamide B from Lyngbya confervoides. Configuration and Asymmetric Synthesis of β-Hydroxy-α-amino Acids by (-)-Sparteine-Mediated Aldol Addition
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(Matrix Presented) Lobocyclamide B, a cyclododecapeptide containing five β-hydroxy-α-amino acid residues, was isolated from Lyngbya confervoides. This is the first reported occurrence of γ-hydroxythreonine in a natural peptide. Optically active β-hydroxy-α-amino acids required for configurational analysis of the title compound were prepared using a novel (-)-sparteine-mediated asymmetric aldol addition of N-(diphenylmethylene)glycine tert-butyl ester to aldehydes. The method is general for aliphatic and aryl aldehydes and notable for operational simplicity.
- MacMillan, John B.,Molinski, Tadeusz F.
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p. 1883 - 1886
(2007/10/03)
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- A new synthesis of enantiomerically pure syn-(S)-β-hydroxy-α-amino acids via asymmetric aldol reactions of aldehydes with a homochiral Ni(II)-glycine/(S)-BPB Schiff base complex
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syn-(S)-β-Hydroxy-α-amino acids were synthesised stereoselectively via elaboration of the asymmetric aldol reactions of aldehydes with a chiral Ni(II)-(S)-BPB/glycine Schiff base complex in the presence of equimolar NaH in THF. The stereoselectivity of the reaction was studied as a function of time, the reaction conditions, the nature of the carbonyl compounds and the base used. The synthetic potential of this asymmetric method was demonstrated in the preparation of syn-(S)-β-hydroxyleucine on a multi-gram scale.
- Belokon, Yuri N.,Kochetkov, Konstantin A.,Ikonnikov, Nikolai S.,Strelkova, Tatiana V.,Harutyunyan, Syuzanna R.,Saghiyan, Ashot S.
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p. 481 - 485
(2007/10/03)
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- Efficient enantioselective synthesis of (2R,3R)- and (2S,3S)-3-hydroxyleucines and their diastereomers through dynamic kinetic resolution
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(2R,3R)- and (2S,3S)-3-Hydroxyleucines, components of cyclodepsipeptides, papuamides and polyoxypeptins, were efficiently synthesized along with their diastereomers from the corresponding β-keto-α-amino acid ester through dynamic kinetic resolution using RuCl2(binap)-catalyzed hydrogenation.
- Makino, Kazuishi,Okamoto, Naoki,Hara, Osamu,Hamada, Yasumasa
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p. 1757 - 1762
(2007/10/03)
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- Preparation and use in amino acid synthesis of a new chiral glycine derivative - (R)- and (S)-tert-Butyl 2-tert-Butyl-4-methoxy-2,5-dihydroimidazole-1-carboxylate (BDI)
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The title compound BDI is prepared on multigram scale, either by resolution of the precursor 2-tert-butylimidazolidin-4-one (from glycine amide and pivalaldehyde) through diastereomeric salts (Scheme 2) or by preparative chromatographic enantiomer separation on a chiral column. Lithiated BDI derivatives are highly nucleophilic species, combining the structural elements of a Li enaminate, of an enolether and of an N-Boc-enaminate (E, G). They react with complete diastereoselectivity (NMR analysis) from the face trans to the tert-butyl group. The electrophiles employed are primary and secondary alkyl, allyl, benzyl, and propargyl halides (Schemes 3 and 5), enoates (in Michael additions, Scheme 7), as well as aliphatic and aromatic aldehydes (in aldol additions, Scheme 8). When a third, exocyclic, stereocenter is formed in these reactions, there is a high degree of enantiomer differentiation (with tac. sec. halides, products 10-12) and of enantiotopic face differentiation (with enoates and aldehydes, products 40-50). The reactions are so clean that highly efficient in-situ double alkylations are feasible, in which the sequence of addition of the two different electrophiles determines the configuration at the newly formed stereogenic center (Scheme 5). In contrast to derivatives of previously reported chiral glycine reagents, the products from BDI are converted to methyl esters of amino acids under mild conditions and without concomitant formation (... and the need for recovery or removal) of a chiral auxiliary; the method is compatible with acid-sensitive side chains in the α-amino acids and α-branched α-amino acids to be synthesized (Schemes 4 and 6). The addition of Li-BDI to aldehydes furnishes, after hydrolysis, α-amino-β-hydroxy acids of erythro configuration (allo-threonine analogs, Scheme 8); a model for the stereochemical course of this reaction (rel. topicity unlike) is proposed, and compared with the corresponding conversions of analogous oxazolidinone and imidazolidinone Li enolates which occur with rel. topicity like.
- Seebach, Dieter,Hoffmann, Matthias
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p. 1337 - 1351
(2007/10/03)
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- Efficient chemoenzymatic synthesis of (2S,3S)-3-hydroxyleucine mediated by immobilised penicillin G acylase
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Immobilised penicillin G acylase (EC 3.5.1.11) has been used in the key step to obtain optically pure (2S,3S)-(+)-hydroxyleucine (ee >99%).
- Fadnavis, Nitin W.,Sharfuddin,Vadivel, S. Kumara,Bhalerao, Uday T.
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p. 3577 - 3578
(2007/10/03)
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- Enzymatic synthesis of β-hydroxy-α-amino acids based on recombinant D- and L-threonine aldolases
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To exploit the enzymatic method for the synthesis of β-hydroxy-α-amino acids, the genes coding for the Escherichia coli L-threonine aldolase (LTA; EC 2.1.2.1) and Xanthomonus oryzae D-threonine aldolase (DTA) were cloned and overexpressed in E. coli through primer-directed polymerase chain reactions. The purified recombinant enzymes were studied with respect to kinetics, specificity, stability, additive requirement, temperature profile, and pH dependency. DTA requires magnesium ion as a cofactor, while LTA needs no metal ions. These enzymes work well in the presence of DMSO with concentration up to 40%, and DMSO-induced rate acceleration of LTA-catalyzed reaction was observed. Both enzymes use pyridoxal phosphate coenzyme to activate glycine to react with a wide range of aldehydes. LTA gave erythro-β-hydroxy-α-L-amino acids with aliphatic aldehydes and the threo isomer with aromatic aldehydes as kinetically controlled products. On the other hand, DTA formed threo-β-hydroxy-α-D-amino acids as kinetically controlled products with aliphatic and aromatic aldehydes but the diastereoselectivity was lower than that of LTA. Under optimal conditions, several β-hydroxy-α-amino acid derivatives (3-hydroxyleucines, γ-benzyloxythreonines, γ-benzyloxymethylthreonines, and poplyoxamic acids) have been stereoselectively synthesized on preparative scales using these enzymes. Also, the tandem use of DTA and phosphatases has made possible the synthesis and separation of D-allo-threonine phosphate and D-threonine.
- Kimura, Teiji,Vassilev, Vassil P.,Shen, Gwo-Jenn,Wong, Chi-Huey
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p. 11734 - 11742
(2007/10/03)
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- Total synthesis of (+)-lactacystin
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A total synthesis of the novel neurotrophic agent (+)-lactacystin (1) has been achieved in 11 steps and 14% overall yield from (2R,3S)-3-hydroxyleucine [(+)-16]. The construction and bioassay of several active analogs are also described. A new asymmetric approach furnished the four stereoisomers of 3-hydroxyleucine, as required starting materials in high overall yield and enantiomeric purity.
- Nagamitsu, Tohru,Sunazuka, Toshiaki,Tanaka, Haruo,Omura, Satoshi,Sprengeler, Paul A.,Smith III, Amos B.
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p. 3584 - 3590
(2007/10/03)
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- Asymmetric Aldol Reactions of Chiral Ni(II)-Complex of Glycine with Aliphatic Aldehydes. Stereodivergent Synthesis of syn-(2S)- and syn-(2R)-β-Alkylserines
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Stereoselectivity of aldol reactions between aliphatic aldehydes and Ni(II)-complex of chiral non-racemic Schiff base of glycine with (S)-o-benzophenone (BPB) in the presence of excess of MeONa, has been studied as a function of time, reaction conditions and nature of an aldehyde.Two salient features of the reaction, very high pseudokinetic syn-(2S)-diastereoselectivity, and dependence of thermodynamic syn-(2R)-diastereoselectivity on the steric bulk of an aldehyde side chain, were disclosed and used for efficient (more than 90percent de and ee) asymmetric synthesis of both syn-(2S) and syn-(2R)-3-alkyl substituted serines.Synthetic potential and reliability of this asymmetric method are demonstrated with the large scale (2-20 g) preparation of enantiomerically pure amino acids.
- Soloshonok, Vadim A.,Avilov, Dimitry V.,Kukhar, Valery P.,Tararov, Vitali I.,Savel'eva, Tatiana D.,et al.
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p. 1741 - 1756
(2007/10/02)
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- Synthesis, resolution and absolute configuration determination of (S)- and (R)-4-formyl-5-hydroxyparacyclophane and its application in the asymmetric synthesis of α-amino acids
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Racemic (R,S)-4-formyl-5-hydroxyparacyclophane (FHPC) was resolved into enantiomers via its Schiff's base with (S)- and (R)-α-phenylethylamine (α-PEAM) and its absolute configuration was determined by an X-ray diffraction structural study.Scalemic FHPC or its derivatives can be used as chiral auxiliaries for the asymmetric synthesis of β-hydroxy-α-amino acids and α-methylphenylalanine with ees ranging mostly from 45 to 98percent.
- Antonov, Dmitri Yu.,Belokon, Yuri N.,Ikonnikov, Nikolai S.,Orlova, Svetlana A.,Pisarevsky, Aleksander P.,et al.
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p. 1873 - 1880
(2007/10/02)
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- Synthesis of (2S,3R)-3-hydroxy leucine: A constituent of lysobactin
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The known 3-O-benzyl-6-deoxy-1,2-O-isopropylidene-α-D-xylohexofuranos-5-ulose was converted stereoselectively to the titled compound 1.
- Yadav,Chandrasekhar,Reddy,Rao
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p. 2749 - 2754
(2007/10/02)
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- An efficient asymmetric synthesis of the four stereoisomers of 3-hydroxyleucine
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The four stereoisomers of 3-hydroxyleucine have been prepared in high overall yield and enantiomeric purity. Key steps include Sharpless asymmetric epoxidation, benzyl isocyanate-induced epoxide opening, and epimerization of an intermediate oxazolidinone ester.
- Sunazuka, Toshiaki,Nagamitsu, Tohru,Tanaka, Haruo,Omura, Satoshi,Sprengeler, Paul A.,Smith III, Amos B.
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p. 4447 - 4448
(2007/10/02)
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- Isolation and Structure Elucidation of Ergokonin A and B; Two New Antifungal Sterol Antibiotics from Trichoderma koningii
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Isolation and structure elucidation by 2D-NMR spectroscopy of the two new antifungal sterol antibiotics ergokonin A (1) and B (2a) from Trichoderma koningii are described.The structures of 1 and 2a are derived from ergosterol and characterized by an 18-carboxy group.In addition ergokonin A (1) is esterified at the 3-hydroxy group with (2S,3S)-3-hydroxyleucine 3-O-sulfate (3c).In the course of structure elucidation of the amino acid residue the stereoisomers of 3-hydroxyleucine N-sulfamate and 3-O-sulfate (3b, c) have been synthesized and characterized by NMR spectroscopy.
- Augustiniak, Hermann,Forche, Edgar,Reichenbach, Hans,Wray, Viktor,Graefe, Udo,Hoefle, Gerhard
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p. 361 - 366
(2007/10/02)
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- ASYMMETRIC ALDOL REACTIONS USING BORON ENOLATES OF CHIRAL OXAZINONES, SYNTHESIS OF L-ALLO-THREONINE
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The boron enolate of oxazinone 1 was allowed to react with acetaldehyde, butanal, and 2-methylpropanal.The reaction proceeded stereoselectively, and in the reaction with acetaldehyde, the reaction afforded a precursor to L-allo-threonine.
- Reno, Daniel S.,Lotz, Bruce T.,Miller, Marvin J.
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p. 827 - 830
(2007/10/02)
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- Color Difference between Diastereomers of the Brucine Salt of Phthaloyl-threo-β-hydroxyleucine
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When phthaloyl-threo-DL-β-hydroxyleucine was resolved using brucine as a resolving agent, yellow and white crystals were obtained. threo-L-Form was obtained from yellow crystals and threo-D-form white ones.The appearance of yellow color is considered to be due to the stacking of benzene ring of phthaloyl group and of brucine molecule.
- Kuwata, Shigeru,Tanaka, Jumpei,Sakamoto, Yoshio,Onda, Norihiro,Yamada, Takashi,Miyazawa, Toshifumi
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p. 2031 - 2032
(2007/10/02)
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- RAPID SYNTHESIS OF β-HYDROXY-α-AMINO ACIDS, SUCH AS L-THREONINE, β-HYDROXYPHENYLALANINE, AND β-HYDROXYLEUCINE, VIA AN APPLICATION OF THE SHARPLESS ASYMMETRIC EPOXIDATION
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The optically active epoxy alcohols 6abc, prepared by a Sharpless kinetic resolution-epoxidation process, were converted to the optically pure β-hydroxy-α-amino acids 1abc in four steps and high overall yield.
- Jung, Michael E.,Jung, Young H.
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p. 6637 - 6640
(2007/10/02)
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- Addition of Chiral Glycine, Methionine, and Vinylglycine enolate Derivatives to Aldehydes and Ketones in the Preparation of Enantiomerically Pure α-Amino-β-hydroxy Acids
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Chiral enolates of imidazolidinones and oxazolidinones from the title amino acids react with carbonyl compounds to afford the corresponding alcohols in excellent yields (see Scheme 5).Furthermore, the addition to aldehydes proceeds with high diastereoselectivity to give, after acid hydrolysis, threo-α-amino-β-hydroxy acids of high enantiomeric purity.Some of the threo-α-amino-β-hydroxy acids prepared in this work are the proteinogenic (S)-threonine (26), the naturally occuring (S)-3-phenylserine (28), and (S)-3-hydroxyleucine (27) as well as the unnatural (S)-4,4,4-rtifluorothreonine (30) and (S)-3-(4-pyridyl)serine (31).The N-methylamide of (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (32), the uniqe amino acid in the immunosuppressive cyclosporine, was prepared by the new method.This report presents also information suggesting that both steric and stereoelectronic effects are responsible for the good stereoselectivities observed.
- Seebach, Dieter,Juaristi, Eusebio,Miller, David D.,Schickli, Christof,Weber, Theodor
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p. 237 - 261
(2007/10/02)
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- Structure of a Peptidal Antibiotic P168 produced by Paecilomyces lilacinus (Thom) Samson
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The peptide antibiotic P168 contained a new amino acid, (2S,4S)-2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (6) and an amine, (S)-N1,N1-dimethylpropane-1,2-diamine (4) along with other unusual amino acids.The structure of the peptide was determined as (I) by in-beam mass spectrometry.
- Isogai, Akira,Suzuki, Akinori,Tamura, Saburo,Higashikawa, Shizuo,Kuyama, Shimpei
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p. 1405 - 1411
(2007/10/02)
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