- Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata
-
Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).
- Iwasaki, Arihiro,Ohtomo, Keisuke,Kurisawa, Naoaki,Shiota, Ikuma,Rahmawati, Yulia,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
-
p. 126 - 135
(2021/01/13)
-
- Isolation and Total Synthesis of Mabuniamide, a Lipopeptide from an Okeania sp. Marine Cyanobacterium
-
The bioassay-guided fractionation of an Okeania sp. marine cyanobacterium collected in Okinawa led to the isolation of the lipopeptide mabuniamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute configuration was determined using Marfey's analysis of the acid hydrolysate of 1. The absolute configuration of 1 was confirmed by total synthesis. Mabuniamide (1) stimulated glucose uptake in cultured rat L6 myotubes. In addition, mabuniamide (1) and its stereoisomer (2) exhibited moderate antimalarial activity.
- Ozaki, Kaori,Iwasaki, Arihiro,Sezawa, Dai,Fujimura, Haruka,Nozaki, Tomoyoshi,Saito-Nakano, Yumiko,Suenaga, Kiyotake,Teruya, Toshiaki
-
p. 2907 - 2915
(2019/10/16)
-
- Isolation, structure elucidation and biological evaluation of lagunamide D: A new cytotoxic macrocyclic depsipeptide from marine cyanobacteria
-
Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migration at the 1,3-diol unit, and the transformation product was named lagunamide D'. The planar structures of both compounds were elucidated using a combination of nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS). The absolute configurations were determined on the basis of enantioselective analysis, modified Mosher's analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure closely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative activity against A549 human lung adenocarcinoma cells, while the structural transformation from the 26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide D' led to a 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis in a dose- and time-dependent manner. Further investigation on the mechanism of action of the lagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent.
- Luo, Danmeng,Putra, Masteria Y.,Ye, Tao,Paul, Valerie J.,Luesch, Hendrik
-
-
- Discovery of Amantamide, a Selective CXCR7 Agonist from Marine Cyanobacteria
-
CXCR7 plays an emerging role in several physiological processes. A linear peptide, amantamide (1), was isolated from marine cyanobacteria, and the structure was determined by NMR and mass spectrometry. The total synthesis was achieved by solid-phase method. After screening two biological target libraries, 1 was identified as a selective CXCR7 agonist. The selective activation of CXCR7 by 1 could provide the basis for developing CXCR7-targeted therapeutics and deciphering the role of CXCR7 in different diseases.
- Liang, Xiao,Luo, Danmeng,Yan, Jia-Lei,Rezaei, Mohammad A.,Salvador-Reyes, Lilibeth A.,Gunasekera, Sarath P.,Li, Chenglong,Ye, Tao,Paul, Valerie J.,Luesch, Hendrik
-
supporting information
p. 1622 - 1626
(2019/03/07)
-
- Odoamide, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Okeania sp.
-
The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the 26-membered cyclodepsipeptide odoamide (1). The gross structure of 1 was determined by 1D and 2D NMR analyses, whereas its absolute stereochemistry was determined using a variety of different methods, including synthesis and chemical degradation followed by chiral HPLC analysis. Notably, odoamide (1) showed potent cytotoxicity against HeLa S3 human cervical cancer cells with an IC50value of 26.3?nM.
- Sueyoshi, Kosuke,Kaneda, Masato,Sumimoto, Shinpei,Oishi, Shinya,Fujii, Nobutaka,Suenaga, Kiyotake,Teruya, Toshiaki
-
p. 5472 - 5478
(2016/08/05)
-
- Ulleungamides A and B, Modified α,β-Dehydropipecolic Acid Containing Cyclic Depsipeptides from Streptomyces sp. KCB13F003
-
Two novel cyclic depsipeptides, ulleungamides A (1) and B (2), were isolated from cultures of terrestrial Streptomyces sp. Their structures were determined by analyses of spectroscopic data and various chemical transformations, including modified Mosher's method, advanced Marfey's method, PGME, GITC derivatizations, and Snatzke's method. Ulleungamides were determined to be a new class of peptides bearing unprecedented units, such as 5-hydroxy-6-methyl-2,3-dehydropipecolic acid, 4,5-dihydroxy-6-methyl-2,3-dehydropipecolic acid, and amino-linked 2-isopropylsuccinic acid. Ulleungamide A displayed growth inhibitory activity against Staphylococcus aureus and Salmonella typhimurium without cytotoxicity.
- Son, Sangkeun,Ko, Sung-Kyun,Jang, Mina,Lee, Jae Kyoung,Ryoo, In-Ja,Lee, Jung-Sook,Lee, Kyung Ho,Soung, Nak-Kyun,Oh, Hyuncheol,Hong, Young-Soo,Kim, Bo Yeon,Jang, Jae-Hyuk,Ahn, Jong Seog
-
supporting information
p. 4046 - 4049
(2015/09/01)
-
- Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.
-
Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Suda, Shoichiro,Suenaga, Kiyotake
-
supporting information
p. 4126 - 4128
(2015/02/19)
-
- Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.
-
Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Suda, Shoichiro,Suenaga, Kiyotake
-
supporting information
p. 4126 - 4128
(2014/07/22)
-
- Lipopeptides from the tropical marine cyanobacterium symploca sp.
-
A collection of the tropical marine cyanobacterium Symploca sp., collected near Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including kimbeamides A-C, kimbelactone A, and tasihalide C. Investigations into a more polar cytotoxic fraction yielded three new lipopeptides, tasiamides C-E (1-3). The planar structures were deduced by 2D NMR spectroscopy and tandem mass spectrometry, and their absolute configurations were determined by a combination of Marfeys and chiral-phase GC-MS analysis. These new metabolites are similar to several previously isolated compounds, including tasiamide (4), grassystatins (5, 6), and symplocin A, all of which were isolated from similar filamentous marine cyanobacteria.
- Mevers, Emily,Haeckl, F. P. Jake,Boudreau, Paul D.,Byrum, Tara,Dorrestein, Pieter C.,Valeriote, Frederick A.,Gerwick, William H.
-
p. 969 - 975
(2014/05/20)
-
- Isolation of ciliatamide D from a marine sponge Stelletta sp. and a reinvestigation of the configuration of ciliatamide A
-
A new lipopeptide, ciliatamide D (1), was isolated from a marine sponge Stelletta sp., collected at Oshimashinsone, together with the known compound ciliatamide A (2). Ciliatamide D (1) is a congener of 2, in which N-Me-Phe is replaced by N-Me-Met(O). Marfey's analysis of the acid hydrolysate of 1 demonstrated that the two constituent amino acids were both in the l-form. This result prompted us to carefully investigate the configuration of 2, resulting in the assignment of the l-form for both residues.
- Imae, Yasufumi,Takada, Kentaro,Okada, Shigeru,Ise, Yuji,Yoshimura, Hiroshi,Morii, Yasuhiro,Matsunaga, Shigeki
-
p. 755 - 758
(2013/06/05)
-
- Cyclic heptapeptides, cordyheptapeptides C-E, from the marine-derived fungus Acremonium persicinum SCSIO 115 and their cytotoxic activities
-
Three new cycloheptapeptides, cordyheptapeptides C-E (1-3), were isolated from the fermentation extract of the marine-derived fungus Acremonium persicinum SCSIO 115. Their planar structures were elucidated on the basis of extensive MS, as well as 1D and 2
- Chen, Ziming,Song, Yongxiang,Chen, Yuchan,Huang, Hongbo,Zhang, Weimin,Ju, Jianhua
-
p. 1215 - 1219
(2012/11/13)
-
- Cyclodepsipeptides, sesquiterpenoids, and other cytotoxic metabolites from the filamentous fungus Trichothecium sp. (MSX 51320)
-
Two new cyclodepsipeptides (1 and 2), two new sesquiterpenoids (3 and 4), and the known compounds guangomide A (5), roseotoxin S, and three simple trichothecenes were isolated from the cytotoxic organic extract of a terrestrial filamentous fungus, Trichothecium sp. The structures were determined using NMR spectroscopy and mass spectrometry. Absolute configurations of the cyclodepsipeptides were established by employing chiral HPLC, while the relative configurations of 3 and 4 were determined via NOESY data. The isolation of guangomide A was of particular interest, since it was reported previously from a marine-derived fungus.
- Sy-Cordero, Arlene A.,Graf, Tyler N.,Adcock, Audrey F.,Kroll, David J.,Shen, Qi,Swanson, Steven M.,Wani, Mansukh C.,Pearce, Cedric J.,Oberlies, Nicholas H.
-
experimental part
p. 2137 - 2142
(2011/12/14)
-
- Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula
-
Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey's method, a modified method based on derivatization with Mosher's reagents and analysis using LC-MS, and the use of 3JH-H coupling constant values, were utilized for the determination of its absolute configuration. Compound 1 is related to the aurilide-class of molecules and it differs mainly in the macrocyclic structure by having a 27 membered ring system due to additional methylene carbon in the polyketide moiety. Lagunamide C displayed potent cytotoxic activity against a panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC50 values ranging from 2.1 nM to 24.4 nM. Compound 1 also displayed significant antimalarial activity with IC50 value of 0.29 μM when tested against Plasmodium falciparum. In addition, lagunamide C exhibited weak anti-swarming activity when tested at 100 ppm against the Gram-negative bacterial strain, Pseudomonas aeruginosa PA01.
- Tripathi, Ashootosh,Puddick, Jonathan,Prinsep, Michele R.,Rottmann, Matthias,Chan, Kok Ping,Chen, David Yu-Kai,Tan, Lik Tong
-
experimental part
p. 2369 - 2375
(2012/02/03)
-
- Porpoisamides A and B, two novel epimeric cyclic depsipeptides from a Florida Keys collection of Lyngbya sp.
-
NMR-guided fractionation of a non-polar extract of a Florida Keys collection of Lyngbya sp. resulted in the isolation of two novel epimeric cyclic depsipeptides, porpoisamides A (1) and B (2). The planar structures of these compounds were determined using NMR spectroscopic techniques. The absolute configurations of amino and hydroxy acid subunits were assigned by enantioselective HPLC analysis. These compounds showed weak cytotoxicity towards HCT-116 colorectal carcinoma and U2OS osteosarcoma cells. The porpoisamides are a unique pair of cyclic depsipeptides that are epimeric at C-2 of the β-amino acid, 3-amino-2-methyloctanoic acid.
- Meickle, Theresa,Gunasekera, Sarath P.,Liu, Yanxia,Luesch, Hendrik,Paul, Valerie J.
-
experimental part
p. 6576 - 6580
(2011/12/15)
-
- PROTEASE INHIBITORS, COMPOSITIONS AND METHODS OF USE
-
This invention relates to grassystatins A, B and C, and their isolated or purified forms. The compounds of the invention are useful as aspartic protease, gamma secretase, or metalloprotease inhibitors. Methods of using the compounds and compositions thereof are also disclosed.
- -
-
Page/Page column 34-35
(2011/01/12)
-
- Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
-
Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+ and Zn 2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.
- Kwan, Jason C.,Ratnayake, Ranjala,Abboud, Khalil A.,Paul, Valerie J.,Luesch, Hendrik
-
experimental part
p. 8012 - 8023
(2011/03/20)
-
- Lagunamides A and B: Cytotoxic and antimalarial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula
-
Lagunamides A (1) and B (2) are new cyclic depsipeptides isolated from the marine cyanobacterium Lyngbya majuscula obtained from Pulau Hantu Besar, Singapore. The planar structural characterization of these molecules was achieved by extensive spectroscopic analysis, including 2D NMR experiments. In addition to Marfey's method and 3JH-H coupling constant values, a modified method based on Mosher's reagents and analysis using LC-MS was deployed for the determination of the absolute configuration. Lagunamides A and B displayed significant antimalarial properties, with IC50 values of 0.19 and 0.91 μM, respectively, when tested against Plasmodium falciparum. Lagunamides A and B also possessed potent cytotoxic activity against P388 murine leukemia cell lines, with IC50 values of 6.4 and 20.5 nM, respectively. Furthermore, these cyanobacterial compounds exhibited moderate antiswarming activities when tested against Pseudomonas aeruginosa PA01.
- Tripathi, Ashootosh,Puddick, Jonathan,Prinsep, Michele R.,Rottmann, Matthias,Tan, Lik Tong
-
supporting information; experimental part
p. 1810 - 1814
(2011/02/28)
-
- Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation
-
In our efforts to exploremarine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure
- Kwan, Jason C.,Eksioglu, Erika A.,Liu, Chen,Paul, Valerie J.,Luesch, Hendrik
-
experimental part
p. 5732 - 5747
(2010/03/24)
-
- Halogenated fatty acid amides and cyclic depsipeptides from an eastern Caribbean collection of the cyanobacterium Lyngbya majuscula
-
A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin a
- Jimenez, Jorge I.,Vansach, Tifanie,Yoshida, Wesley Y.,Sakamoto, Bryan,Poerzgen, Peter,Horgen, F. David
-
supporting information; experimental part
p. 1573 - 1578
(2010/03/31)
-
- Homotyrosine-containing cyanopeptolins 880 and 960 and anabaenopeptins 908 and 915 from Planktothrix agardhii CYA 126/8
-
Two homotyrosine-bearing cyanopeptolins are described from Planktothrix agardhii CYA 126/8. The compounds feature a common homotyrosine-containing cyclohexadepsipeptide and differ by sulfation of an exocyclically located 2-O-methyl-D-glyceric acid residue. In addition we describe two anabaenopeptins, which contain two homotyrosine residues, one of which is N-methylated. The anabaenopeptins have a common cyclopentapeptide portion and differ in the amino acid linked to it via an ureido bond, arginine and tyrosine, respectively.
- Okumura, Hilary S.,Philmus, Benjamin,Portmann, Cyril,Hemscheidt, Thomas K.
-
supporting information; experimental part
p. 172 - 176
(2009/06/27)
-
- Carriebowmide, a new cyclodepsipeptide from the marine cyanobacterium Lyngbya polychroa
-
The new cyclodepsipeptide carriebowmide (1), which contains two rare amino acids, 3-amino-2-methylhexanoic acid and methionine sulfoxide, was isolated from the fish-deterrent lipophilic extract of the marine cyanobacterium Lyngbya polychroa, collected from the fore reef near the Smithsonian field station at Carrie Bow Cay, Belize. Its planar structure was determined by NMR spectroscopic techniques. The absolute stereochemistry of the hydroxy acid and all α-amino acid-derived units was ascertained by chiral HPLC analysis of the acid hydrolysate. The stereochemistry of the β-amino acid moiety, 3-amino-2-methylhexanoic acid, was established by Marfey analysis of the acid hydrolysate.
- Gunasekera, Sarath P.,Ritson-Williams, Raphael,Paul, Valerie J.
-
experimental part
p. 2060 - 2063
(2009/09/06)
-
- Resolution of racemic N-benzyl α-amino acids by liquid-liquid extraction: A practical method using a lipophilic chiral cobalt(III) salen complex and mechanistic studies
-
The efficient resolution of racemic N-benzyl α-amino acids (N-Bn-AA) has been achieved by a liquid-liquid extraction process using the lipophilic chiral salen-cobalt(III) complex [CoIII(3)(OAc)]. As a result of the resolution by extraction, one enantiomer (S) of the N-benzyl α-amino acid predominated in the aqueous phase, while the other enantiomer (R) was driven into the organic phase by complexation to cobalt. The complexed amino acid (R) was then quantitatively released by a reductive (CoIII→Co II) counter-extraction with aqueous sodium dithionite or L-ascorbic acid in methanol. The reductive cleavage allowed to recover the [Co II(3)] complex in good yield, which could be easily re-oxidized to [CoIII(3)(OAc)] with air/AcOH and reused with essentially no loss of reactivity and selectivity. Investigation on the nitrogen substitution indicates that the presence of a single benzyl group on the amino acid nitrogen is important to obtain high enantioselectivity in the extraction process. The kinetic vs. thermodynamic nature of the resolution process was also investigated with an enantiomeric exchange experiment, which shows that the liquid-liquid extraction with [CoIII(3)-(OAc)] is an equilibrium process operating under thermodynamic control. In the absence of a suitable crystal structure of the [CoIII(3)(N-Bn-AA)] complexes, computational and spectroscopic studies were used to investigate how the N-benzyl α-amino acids are accommodated in the "binding pocket" of the chiral cobalt complex. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Dzygiel, Pawel,Reeve, Toby B.,Piarulli, Umberto,Krupicka, Martin,Tvaroska, Igor,Gennari, Cesare
-
supporting information; experimental part
p. 1253 - 1264
(2009/04/07)
-
- Synthesis of optically active α-methylamino acids and amides through biocatalytic kinetic resolution of amides
-
Catalyzed by Rhodococcus sp. AJ270, a nitrile hydratase and amidase containing microbial whole-cell catalyst, under very mild conditions, a number of racemic α-methylamino amides were resolved into the corresponding optically active (S)-(+)-α-methylamino acids and (R)-(-)-α- methylamino amides. The steric requirement of the amidase against α-amino phenylacetamides bearing methyl group(s) at α-amino nitrogen and/or α-carbon was also studied. Coupled with the chemical hydrolysis of amide, the biotransformation process provided a direct synthesis of α-methylamino acids in both enantiomeric forms from readily available racemic amides.
- Wang, Mei-Xiang,Liu, Jun,Wang, De-Xian,Zheng, Qi-Yu
-
p. 2409 - 2416
(2007/10/03)
-
- The total synthesis and stereochemical revision of yanucamide A
-
(Matrix presented) The first total synthesis of yanucamide A is reported via amide and ester couplings of the key components. This synthesis has established the configuration at the previously ambiguous 3-position, and also revised the stereochemistry at the 22-position, to give 3S,12S,17S,22S for the natural product.
- Xu, Zhengshuang,Peng, Yungui,Ye, Tao
-
p. 2821 - 2824
(2007/10/03)
-
- (3R,6R)-4-methyl-6-(1 -methylethyl)-3-phenylmethyl-perhydro-1,4-oxazine-2,5-dione: An apoptosis-inducer from the fruiting bodies of Isaria japonica
-
(3R,6R)-4-Methyl-6-(1-methylethyl)-3-phenylmethylperhydro1,4-oxazine-2,5- dione (1) was isolated from the fruiting bodies of Isaria japonica as an apoptosis-inducing agent. The complete structural assignment of the compound was accomplished on the basis of spectroscopic methods and chemical transformations. Compound 1 induced apoptotic cell death of the human leukemia cells (HL-60) in a dose-dependent manner, ranging from 5.0 μg/ml to 100.0 μg/ml.
- Oh, Hyuncheol,Kim, Taewan,Oh, Gi-Su,Pae, Hyun-Ock,Hong, Kyung-Hwan,Chai, Kyu-Yun,Kwon, Tae-Oh,Chung, Hun-Taeg,Lee, Ho-Sub
-
p. 345 - 348
(2007/10/03)
-
- Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids
-
Full details are provided for an exceedingly practical method to synthesize D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water-dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.
- Myers, Andrew G.,Gleason, James L.,Yoon, Taeyoung,Kung, Daniel W.
-
p. 656 - 673
(2007/10/03)
-
- NITROGEN ALKYLATION OF SCHIFF BASES AND AMIDINES AS A ROUTE TO N-ALKYL AMINO ACIDS
-
Schiff base and amidine esters 3 are alkylated and then hydrolyzed to yield N-alkyl amino acids 4 in 41-75percent yield with hight to complete retention of optical activity.
- O'Donnell, Martin J.,Bruder, William A.,Daugherty, Byron W.,Liu, Deshan,Wojciechowski, Krzisztof
-
p. 3651 - 3654
(2007/10/02)
-