- Symplocin A, a linear peptide from the bahamian cyanobacterium symploca sp. configurational analysis of N, N -dimethylamino acids by chiral-phase HPLC of naphthacyl esters
-
The absolute stereostructures of the components of symplocin A (3), a new N,N-dimethyl-terminated peptide from the Bahamian cyanobacterium Symploca sp., were assigned from spectroscopic analysis, including MS, 2D NMR, and Marfey's analysis. The complete a
- Molinski, Tadeusz F.,Reynolds, Kirk A.,Morinaka, Brandon I.
-
experimental part
p. 425 - 431
(2012/07/13)
-
- New potential renin inhibitors with dipeptide replacements in the molecule
-
A series of eight non-peptidic potential renin inhibitors have been designed and synthesized. All of them contain dipeptide replacement: (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) in their molecules. Four among them comprise two additional analogs of dipeptide: (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta). All of the synthesized compounds contain also hydrophobic portions to receive a moderate lipophilicity of the molecules. Inhibitory activity of the compounds was measured in vitro by HPLC determination of Leu-Val-Tyr-Ser released from the N-acetyltetradecapeptide substrate by renin in the presence of the inhibitor. Asp-α(OEt)-(S,S)-ACHPA-εAhx-Iaa (23) shows inhibitory activity (7%) at the concentration of 1.0 × 10-2 M. The other synthesized compounds show no inhibitory activity up to this concentration.
- Winiecka, Iwona,Dudkiewicz-Wilczynska, Jadwiga,Roman, Iza,Paruszewski, Ryszard
-
scheme or table
p. 367 - 374
(2011/08/04)
-
- Strict reagent control in the asymmetric allylboration of N-TIPS-α-amino aldehydes with the B-allyl-10-TMS-9-borabicyclo[3.3.2] decanes
-
(Chemical Equation Presented) The allylboration of enantiomerically pure N-triisopropylsilyl-α-amino aldehydes (2) with B-allyl-10-trimethylsilyl- 9-borabicyclo[3.3.2]decanes (1) proceeds cleanly at -78 °C, exhibiting essentially complete reagent control. After an oxidative workup, an HOAc-mediated N→O TIPS rearrangement facilitates the clean formation of stable O-TIPS protected β-amino alcohol derivatives 3 which are isolated in 60-83% yields in >96% de and >99% ee. For the leucinal series (R = i-Bu), an efficient entry to either statine (8aSS) or epi-statine (8aRS) is reported illustrating the versatility of this potent 1/2 combination.
- Soto-Cairoli, Buddy,Soderquist, John A.
-
supporting information; experimental part
p. 401 - 404
(2009/07/04)
-
- High antiplasmodial activity of novel plasmepsins I and II inhibitors
-
The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, whi
- Dell'Agli, Mario,Parapini, Silvia,Galli, Germana,Vaiana, Nadia,Taramelli, Donatella,Sparatore, Anna,Liu, Peng,Dunn, Ben M.,Bosisio, Enrica,Romeo, Sergio
-
p. 7440 - 7449
(2007/10/03)
-
- Intramolecular nucleophilic epoxidation of γ-amino-α,β- unsaturated esters with an N-hydroperoxymethyl group
-
Intramolecular nucleophilic epoxidation reactions of γ-amino-α, β-unsaturated esters have been studied for the first time with a hydroperoxymethyl group attached to the nitrogen atom. The epoxidation was fast under mild basic conditions and highly anti se
- Yoo, Dongwon,Kim, Hyeonjeong,Kim, Young Gyu
-
p. 1707 - 1710
(2007/10/03)
-
- A stereodivergent approach to syn- and anti-β-hydroxy-γ-amino acids. Enantioselective synthesis of N-Boc-statine and N-Boc-3-epistatine mediated by sulfoxides
-
Asymmetric syntheses of the syn- and anti-stereoisomers of N-Boc statine, based on the stereodivergent reduction of a single sulfoxide 5, derived from N-Boc-L-leucine, are reported.
- Yuste, Francisco,Diaz, Angel,Ortiz, Benjamin,Sanchez-Obregon, Ruben,Walls, Fernando,Garcia Ruano, Jose L.
-
p. 549 - 554
(2007/10/03)
-
- An Epoxide Ring-Opening Reaction via Hypervalent Silicate Intermediate: Synthesis of Statine
-
The azide- and cyanide-opening reaction of epoxide with TBAF and TMSN 3 in THF or TBAF and TMSCN in MeCN occurred regioselectively to afford β-hydroxy azides and cyanides in good yield. These hypervalent silicates have been shown to be highly effective as nucleophilic azide and cyanide donors under mild conditions. This methodology has been applied to the preparation of statine.
- Konno, Hiroyuki,Toshiro, Emi,Hinoda, Naoyuki
-
p. 2161 - 2164
(2007/10/03)
-
- Efficient synthesis of unsymmetrically disubstituted ferrocenes: Towards electrochemical dipeptide-Fc-biosensors
-
Unsymmetrically disubstituted ferrocenes (1a, 1b), electrochemical dipeptide-Fc-biosensors, were synthesized by a straightforward synthetic method from 1,1′-ferrocenedicarboxylic acid. In addition, an efficient solution synthesis of pentapeptide (2) was reported.
- Xu, Yiming,Kraatz, Heinz-Bernhard
-
p. 2601 - 2603
(2007/10/03)
-
- A synthetic approach to 3-hydroxy 4-substituted carboxylic acids based on the stereoselective reduction of 1-trimethylsilyl-1-alkyn-3-ones
-
The oxazaborolidine-mediated reduction of chiral, 4-substituted 1-trimethylsilyl-1-alkyn-3-ones followed by hydroboration affords syn or anti 3-hydroxy 4-substituted carboxylic acids, common substructures of a number of biologically active macrolides, peptides and depsipeptides, with high control on the new C(3) stereocenter. This strategy has been applied to the synthesis of (3S,4S)-3-hydroxy-4-methylheptanoic acid and of N-Boc-statine, constituents of permentin A and pepstatin, respectively. (C) 2000 Elsevier Science Ltd.
- Alemany, Carme,Bach, Jordi,Garcia, Jordi,López, Marta,Rodríguez, Ana B.
-
p. 9305 - 9312
(2007/10/03)
-
- A novel Wittig reaction of oxazolidinones: Stereospecific synthesis of N-BOC-(3S,4S)-statine and N-BOC-(3S,4S)-AHPPA
-
Stereospecific synthesis of N-BOC-(3S,4S)-Statine and N-BOC-(3S,4S)- AHPPA is achieved via a novel Wittig reaction of oxazolidinones in an efficient manner.
- Vidyasagar Reddy,Venkat Rao,Iyengar
-
p. 775 - 776
(2007/10/03)
-
- A versatile approach to N-Boc-statine and N-Boc-norstatine based on the reduction of 1-trialkylsilyl acetylenic ketones. Strong remote effect of the C(1) substituent on the stereoselectivity
-
(formula presented) An efficient, unified approach to chiral, protected β-hydroxy γ-amino and α-hydroxy β-amino acids derived from Boc-L-leucine has been accomplished on the basis of the oxazaborolidine-controlled, stereoselective reduction of 1-trialkyls
- Alemany, Carme,Bach, Jordi,Farra?s, Jaume,Garcia, Jordi
-
p. 1831 - 1834
(2008/02/11)
-
- New renin inhibitors containing aliphatic or aromatic amides at the C-terminus
-
Five renin inhibitors, Iva-Pro-Phe(4-OMe)-MeLeu-Sta-εAhx-IAA (18), Iva-εAhx-Phe(4-OMe)-MeLeu-Sta-εAhx-IAA (23), H-εAhx-Phe(4-OMe)-His-Sta-εAhx-FBZA (36), H-εAhx-Phe(4-OMe)-His-Sta-εAhx-MBZA (45), and H-Phe (4-OMe)-His-Sta-εAhx-FBZA (48) have been synthesized in search of structures of improved biological properties. All synthesized inhibitors were resistant to chymotrypsin activity. Inhibitors 18 and 23 were insoluble in buffers, pH 7.4 and 2.0, 36, 45 and 48 were very good soluble in buffer pH 2.0 and poorly in buffer pH 7.4. Experimentally determined 1-octanol/pH 7.4 buffer partition coefficients (log P) of 36, 45 and 48 were above 1. Log P values of 18, 23, 36, 45 and 48 were 6.57, 6.91, 2.48, 2.09 and 2.00 respectively. The inhibitory potency in vitro of 18, 23, 36, 45 and 48 expressed as IC50 was 7.5 · 10-5, 5.0 · 10-6, 7.5 · 10-3, 1.0 · 10-4 and 2.5 · 10-5 M/l respectively.
- Paruszewski,Jaworski,Tautt,Dudkiewicz
-
p. 206 - 209
(2007/10/03)
-
- Stereoselective synthesis of (-)-N-Boc-statine and (-)-N-Boc-norstatine
-
An efficient synthesis of optically pure N-Boc-statine (9) and N-Boc-norstatine (11) has been developed via a syn selective Grignard reaction of N-Boc-leucinal with allyl- or vinylmagnesium bromide.
- Veeresha,Datta, Apurba
-
p. 5223 - 5224
(2007/10/03)
-
- Process for the stereospecific preparation of 5-(1-hydroxy-2-urethanethylidene)-2,-dimethyl-1,3-dioxane-4,6-dione derivatives, which are precursors of chiral tetramic acid derivatives
-
The invention relates to a process for the preparation of 5-(1-hydroxy-2-urethanethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione derivatives, which are precursors of chiral tetramic acid derivatives. According to this process, an N-urethane-protected α-amino acid N-carboxy-anhydride is reacted with Meldrum's acid in an inert organic solvent medium in the presence of a tertiary amine. This process makes it possible to conserve the chirality of the starting material and in particular to simplify the synthesis of 4-amino-3-hydroxy acids and the derivatives thereof via the tetramic acid route.
- -
-
-
- Synthesis of Chiral Urethane N-Alkoxycarbonyl Tetramic Acids from Urethane N-Carboxyanhydrides (UNCAs)
-
The synthesis of chiral N-protected tetramic acid derivatives which are precursors of β-hydroxy γ-amino acid under mild conditions is described.Reaction of urethane-N-carboxyanhydrides (UNCAs) with Meldrum's acid in the presence of a tertiary amine, follo
- Fehrentz, Jean-Alain,Bourdel, Elisabeth,Califano, Jean-Christophe,Chaloin, Oliveir,Devin, Chantal,et al.
-
p. 1557 - 1560
(2007/10/02)
-
- Sterically congested chiral N-acetyl 2-oxazolidinone as acetyl enolate equivalents in stereoselective aldol reactions
-
Sterically constrained and highly congested N-acetyl-DMAOx (1a) serves well as a useful chiral acetyl enolate equivalent which permits a diastereoselective and direct approach to 'acetate' aldols (2) including statine derivative.
- Otsuka,Ishizuka,Kimura,Kunieda
-
p. 748 - 750
(2007/10/02)
-
- Chiral synthons for 2-amino alcohols. Facile preparation of optically active amino hydroxy acids of biological interest
-
A promising method for the versatile synthesis of chiral 2-amino alcohols is provided by the enantioselective functionalization of the olefinic moiety of the simple heterocycle, 2-oxazolone, involving a stereodefined introduction of easily replaceable groups followed by stepwise substitution. Versatility of this method is shown in chiral synthesis of unusual hydroxy amino acids such as statine and hydroxyglutamic acid, which are the key components of bioactive peptides.
- Ishibuchi, Seigo,Ishizuka, Tadao,Kunieda, Takehisa
-
p. 1841 - 1852
(2016/02/17)
-
- A Facile Synthesis of N-Protected Statine and Analogues via a Lipase-Catalyzed Kinetic Resolution
-
A new synthesis of N-protected statine 4a and its analogue 4b is presented. cis-(+/-)-Butyric acid 2-isobutyl-5-oxopyrrolidin-3-yl ester (10a) and cis-(+/-)-butyric acid 2-benzyl-5-oxopyrrolidin-3-yl ester (10b) were prepared from methyl (E)-4-chloro-3-me
- Baenziger, Markus,McGarrity, John F.,Meul, Thomas
-
p. 4010 - 4012
(2007/10/02)
-
- Stereoselective vinylation of amino aldehydes using 2-trimethylsilylethylidentriphenylphosphorane
-
2-Trimethylsilylethylidentriphenylphosphorane reacts stereoselectively with α-amino aldehydes giving the Cram chelation controlled product of vinylation of the carbonyl group. The olefinic 1,2-amino alcohols obtained with this reaction are important inter
- Franciotti,Mann,Taddei
-
p. 6783 - 6786
(2007/10/02)
-
- Syntheses and reactions of silyl carbamates. 2. A new mode of cyclic carbamate formation from tert-butyldimethylsilyl carbamate
-
Stereoselective construction of 1,2 and 1,3 amino hydroxyl systems was achieved by the intramolecular trapping of the N-tert-butyldimethylsilyloxycarbonyl species (silyl carbamate) activated by fluoride ion. The reaction of the silyl carbamate with 1,2-sy
- Sakaitani, Masahiro,Ohfune, Yasufumi
-
p. 1150 - 1158
(2007/10/02)
-
- 1,2,4-Triazolopyrazine Derivatives with Human Renin Inhibitory Activity. 1. Synthesis and Biological Properties of Alkyl Alcohol and Statine Derivatives
-
A series of 1,2,4-triazolopyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) transition-state mimetics, have been prepared.Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-pyrazin-3-yl>-3-(3-pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen.Compounds 12m, 12o, and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration.On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion.The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.
- Roberts, David A.,Bradbury, Robert H.,Brown, David,Faull, Alan,Griffiths, David,et al.
-
p. 2326 - 2334
(2007/10/02)
-
- Process for the stereospecific synthesis of optically pure 4-amino-3-hydroxycarboxylic acid derivatives
-
The process described makes it possible to obtain optically pure 4-amino-3-hydroxycarboxylic acids by means of a series of stereoselective steps. The starting material is an alpha-amino acid in the L or D configuration, with which Meldrum's acid is reacted. The resulting pyrrolone derivative is reduced prior to opening of the pyrrolidine ring. The invention also relates to the new products obtained by the said process and to the pyrrolone derivatives obtained as intermediates.
- -
-
-
- Design, Structure-Activity, and Molecular Modeling Studies of Potent Renin Inhibitory Peptides Having N-Terminal Nin-For-Trp (Ftr): Angiotensinogen Congeners Modified by P1-P1' Phe-Phe, Sta, LeuΨVal or LeuΨVal Substitutions
-
A structure-conformation-activity investigation of several angiotensinogen (ANG) based inhibitors of human renin modified by either Phe-Phe, Sta, LeuΨVal, or LeuΨVal at the P1-P1' cleavage site and P5 Trp(Nin-For) (Ftr) was performed.Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 x 10-8 M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies.Substitution of the P1-P1' Phe-Phe in compound 1 by Sta effected a 1000-fold increase in biological potency for the resultant octapeptide Ac-Ftr-Pro-Phe-His-Sta-Val-Ftr-NH2 (10; KI = 6.7 x 10-11 M).Kinetic analysis of compound 10 showed it to be a competitive inhibitor of human renin catalyzed proteolysis of human ANG.Chemical modifications of the compounds 1 and 10 were evaluated on the basis of comparative human plasma renin inhibitory activities (IC 50 values) in vitro.Carboxy-terminal truncation studies on compound 10 showed that the P2' Val and P3' Ftr residues could both be eliminated without significant loss (ca. 10-fold) in renin inhibitory activity as exemplified by the pentapeptide Ac-Ftr-Pro-Phe-His-Sta-NH2 (12; IC 50 = 3.8 x 10-9 M).In addition, the corresponding P1-P1' LeuψVal and LeuψVal derivatives of compound 12 were potent renin inhibitors: Ac-Ftr-Pro-Phe-His-LeuψVal-NH2 (13; IC 50 = 3.1 x 10-10 M) and Ac-Ftr-Pro-Phe-His-LeuψVal-NH2 (14; IC 50 = 2.1 x 10-8 M).The structure-conformation-activity properties of the N-terminal Ftr substitution of these human renin inhibitors was examined by (1) comparative analysis of several analogues of 1 and Ac-Ftr-Pro-Phe-His-Sta-Ile-NH2 (17; IC 50 = 1.0 x 10-10 M) having P5 site modifications by Trp, His, D-Ftr and D-His, (2) deletion of the N-terminal Ftr residue from compound 12 and 17, to provide Ac-Pro-Phe-His-Sta-Ile-NH2 (16; IC 50 = 3.1 x 10-8 M) and Ac-Pro-Phe-His-Sta-NH2 (15; IC 50 = 5.6 x 10-6 M), and (3) computer modeling and dynamic studies of compounds 1 and 17 bound to CKH-RENIN, a simulated human renin model, which were focused on identifying potentional intermolecular interactions of their common P5-P2 sequence, Ac-Ftr-Pro-Phe-His, at the enzyme active site.Finally, the human renin specificity of selected congeners of compound 10 were determined by comparison to porcine kidney renin in vitro.
- Sawyer, Tomi K.,Pals, Donald T.,Mao, Boryeu,Staples, Douglas J.,Vaux, Anne E. de,et al.
-
-
- A NEW MODE OF CYCLIC CARBAMATE FORMATION VIA tert.-BUTYLDIMETHYLSILYL CARBAMATE. STEREOSELECTIVE SYNTHESES OF STATINE AND ITS ANALOGUE
-
Stereoselective construction of 1,2- and 1,3-amino hydroxyl systems was carried out using SN2' (initiated by AgF or AgF-Pd(II)) cyclic carbamate formations from tert.-butyldimethyl silyl carbamates.This method was applied to the syntheses of st
- Sakaitani, Masahiro,Ohfune, Yasufumi
-
p. 3987 - 3990
(2007/10/02)
-
- Stereospecific Synthesis of N-Protected Statine and Its Analogues via Chiral Tetramic Acid
-
The condensation of a chiral N-protected amino acid with Meldrum's acid in the presence of isopropenyl chloroformate (IPCF) and of 4-N,N-dimethylaminopyridine (DMAP) has been examined.The cyclisation of the reaction product, by heating in an organic solve
- Jouin, Patrick,Castro, Bertrand,Nisato, Dino
-
p. 1177 - 1182
(2007/10/02)
-