- Ahmpatinin iBu, a new HIV-1 protease inhibitor, from Streptomyces sp. CPCC 202950?
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Ahmpatinin iBu (1) and statinin iBu (2), two new linear peptides, a novel pyrrolidine derivative, ()-(S)-2-[3-(6-methylheptanamido)-2-oxopyrrolidin-1-yl] acetic acid (3), and three known pepstatin derivatives (4–6) along with their corresponding methanolysis artifacts (7–9) were isolated from Streptomyces sp. CPCC 202950. Their structures were elucidated on the basis of extensive spectroscopic data using Marfey's analysis, chiral-phase HPLC, and ECD and OR calculation to determine the absolute configurations. Compound 1 contains an unusual amino acid, 4-amino-3-hydroxy-5-(4-methoxyphenyl)pentanoic acid (Ahmppa), and 3 is the first natural product with a 2-(3-amino-2-oxopyrrolidin-1-yl)acetic acid system. Compounds 1, 2, and 4–9 are HIV-1 protease inhibitors. In particular, ahmpatinin iBu (1) exhibits significant inhibitory activity against HIV-1 protease with an IC50 value of 1.79 nM. A preliminary structure–activity relationship is discussed.
- Chen, Ming-Hua,Chang, Shan-Shan,Dong, Biao,Yu, Li-Yan,Wu, Ye-Xiang,Wang, Ren-Zhong,Jiang, Wei,Gao, Zeng-Ping,Si, Shu-Yi
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- The N-hydroxymethyl group for stereoselective conjugate addition: application to the synthesis of (-)-statine.
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[reaction: see text] Efficient synthesis of enantiomerically pure (-)-statine was achieved with the stereoselective intramolecular conjugate addition of the hydroxyl group tethered to the amino group of a configurationally stable N-Boc-L-leucinal derivative.
- Yoo, Dongwon,Oh, Joon Seok,Kim, Young Gyu
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- FUNCTIONALIZED FLUORINE CONTAINING PHTHALOCYANINE MOLECULES
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Functionalized fluorine containing phthalocyanine molecules, methods of making, and methods of use in diagnostic applications and disease treatment are disclosed herein. In some embodiments, the fluorine containing phthalocyanine molecules are functionalized with a reactive functional group or at least one cancer-targeting ligand (CTL). The CTL can facilitate more efficient binding and/or internalization to a cancer cell than to a healthy cell. The CTL can inhibit expression of oncoprotein in some embodiments. The pthalocyanine moiety can be used in diagnostic applications, such as fluorescence labeling of a cancer cell, and/or treatment applications, such as catalyzing formation of a reactive oxygen species (ROS) which can contribute to cell death of a cancer cell.
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- Regioselective Baeyer-Villiger lactonization of 2-substituted pyrrolidin-4-one. Synthesis of statine
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Nine 2-substituted pyrrolidin-4-ones 4a-i were obtained via a series of functional group transformation of known prolinol 5 by facile six kinds of methodologies. The target structure of 1,3-amino alcohols 2a-i was constructed in the regioselective Baeyer-
- Chang, Meng-Yang,Kung, Yung-Hua,Chen, Shui-Tein
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p. 4865 - 4870
(2007/10/03)
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- Unusual regioselection in the Mitsunobu reactions of syn-2,3-dihydroxy esters: Synthesis of statine and its diastereomer
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Mitsunobu reactions of syn-2,3-dihydroxy esters exhibit a complete regioselection for the β-hydroxyl group. Benzoylation, azidation, and tosylation have been performed under these conditions. β-Functionalizations of syn-2,3-dihydroxy esters are uncommon, and the Mitsunobu reactions are complementary to other diol chemistries in the regioselection. In addition, the configurational inversion accompanying the Mitsunobu protocol offers a means for diastereochemical diversity, as exemplified by a synthesis of statine and its anti diastereomer. These findings will further expand the synthetic utilities of the Sharpless AD process.
- Ko, Soo Y.
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p. 2689 - 2691
(2007/10/03)
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- Diastereoselective synthesis of enantiopure γ-amino-β-hydroxy acids by Reformatsky reaction of chiral α-dibenzylamino aldehydes
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N,N-Dibenzylamino aldehydes 1 react with Reformatsky's reagent leading to anti-γ-dibenzylamino-β-hydroxy esters 2 as the major stereoisomers. Treatment of 2 with TFA followed by hydrogenolysis on Pearlman's catalyst yields the corresponding γ-amino-β-hydroxy acids 10. Contrarily, some N-butoxycarbonyl (Boc) amino aldehydes lead to syn-γ-tert-butoxycarbonylamino-β-hydroxy esters as the major product.
- Andrés, José M,Pedrosa, Rafael,Pérez, Alberto,Pérez-Encabo, Alfonso
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p. 8521 - 8530
(2007/10/03)
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- Reagent control in the aldol addition reaction of chiral boron enolates with chiral aldehydes. Total synthesis of (3S,4S)-statine
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Boron enolates bearing menthone-derived chiral ligands are capable of fair to excellent diastereocontrol in their reactions with chiral aldehydes. Thioester-derived (better than ketone derived) enolates are able to control aldol stereochemistry irrespective of the aldehyde preferences. With thioacetate-derived chiral enolates and enantiopure N,N-dibenzyl α-amino aldehydes, either the 3,4- anti or the 3,4-syn aldol adduct can be obtained with very high diastereoselectivity just by changing the chiral boron ligand configuration. The above procedure was used for a stereoselective total synthesis of (3S,4S)-statine.
- Gennari, Cesare,Moresca, Daniela,Vulpetti, Anna,Pain, Gilles
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p. 5593 - 5608
(2007/10/03)
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- 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
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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.
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- Diastereo- und enantioselektive Synthese von 1,2-Aminoalkoholen aus Glycolaldehyd-Hydrazonen - asymmetrische Synthese von (R,R)-Statin
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Stichworte: Aminoalkohole * Asymmetrische Synthesen * Hydrazone * Nucleophile Additionen * Statine
- Enders, Dieter,Reinhold, Ulrich
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p. 1332 - 1334
(2007/10/02)
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- A New Method for Hydroxymethylene Peptide Isostere Synthesis: Asymmetric Synthesis of Statine
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The asymmetric synthesis of (-)-Statine is described.The key step of the synthesis involves the coupling of hemi-acetal 6 with the ketene silyl acetal of methyl acetate.
- Williams, Robert M.,Colson, Pierre-Jean,Zhai, Weixu
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p. 9371 - 9374
(2007/10/02)
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- A simple total synthesis of naturally occurring hydroxy-amino acids by enzymatic kinetic resolution
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Both optically pure enantiomers of GABOB and isoserine were obtained by enzymatic kinetic resolution of acetylated precursors in three or four steps. The key intermediates were cyanohydrins available from simple aldehydes. This procedure can be applied to other unusual hydroxy amino acids widely distributed in biologically important peptides.
- Lu,Miet,Kunesch,Poisson
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p. 893 - 902
(2007/10/02)
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- DIVERGENT ASYMMETRIC SYNTHESIS OF erythro- OR threo-3-AZIDO-1,2-EPOXIDES FROM THE SAME 2,3-EPOXY-1-ALKANOL. A CONVENIENT SYNTHESIS OF STATINE AND ITS 3-EPIMER
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A 2,3-epoxy-1-alkanol (obtained by Sharpless asymmetric epoxidation of the corresponding allylic alcohol), O-protected with a 2-methoxypropyl group, undergoes gighly regioselective oxirane ring opening by attack of azide ion at C-3 to afford a monoprotect
- Bertelli, Lucia,Fiaschi, Rita,Napolitano, Elio
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p. 521 - 524
(2007/10/02)
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- Chiral synthons for 2-amino alcohols. Facile preparation of optically active amino hydroxy acids of biological interest
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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
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p. 1841 - 1852
(2016/02/17)
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- AN ENANTIOSPECIFIC AND VERSATILE SYNTHESIS OF STATINE
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A short, enantiospecific synthesis of statine is described, starting from a readily available aldehyde.The control of chirality was effected by using the Sharpless asymmetric epoxidation procedure.
- Saiah, M.,Bessodes, M.,Antonakis, K.
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p. 111 - 112
(2007/10/02)
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- Synthesis of DL-Statine and DL-4-Amino-3-hydroxy-4-phenylbutanoic Acids via the Isoxazoline Route
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1,3-Dipolar cycloaddition of chloronitrile oxide to N-allyltrichloroacetamides and subsequent reductive cleavage of the 3-methoxy-substituted isoxazolines gives methyl 3-hydroxy-4-trichloroacetamido esters which by acidic hydrolysis give the corresponding
- Halling, Karen,Torssell, Kurt B. G.,Hazell, Rita G.
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p. 736 - 741
(2007/10/02)
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- A highly stereoselective synthesis of (3S,4S)-statine and (3S,4S)-cyclohexylstatine
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The title compounds, which are synthetic intermediates of renin inhibitors, could be prepared from (S)-leucine and (S)-phenylalanine, respectively, by employing highly stereoselective aldol reactions of O-methyl-O-trimethylsilyl ketene acetal with an (S)-
- Takemoto,Matsumoto,Ito,Terashima
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p. 2425 - 2428
(2007/10/02)
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- A stereoselective synthesis of (3S,4S) statine and related compounds
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(3S,4S)Statine and (3S,4S)AHPPA were synthesized efficiently using a highly stereoselective iodocyclocarbamation of the chiral Z-olefins 6 and 6b derived from the correspondent α-aminoacids.
- Misiti,Zappia
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p. 7359 - 7362
(2007/10/02)
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- DIASTEREOSPECIFIC SYNTHESIS OF (-)-STATINE
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Reductive deoxygenation at quarternary α-carbon of α-hydroxy lactam was found to preceed under mild condition.Making an advantage of this procedure, (-)-statine was synthesized from L-malic acid in a diastereospecific manner.
- Ohta, Tomihisa,Shiokawa, Sojiro,Sakamoto, Rumiko,Nozoe, Shigeo
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p. 7329 - 7332
(2007/10/02)
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- An expeditious synthesis of (3S,4S)-statine and (3S,4S)cyclohexylstatine
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The title synthesis could be accomplished by employing highly stereoselective aldol reaction of O-methyl-O-trimethylsilyl ketene acetal with the (S)-α-amido aldehyde (2) in the presence of titanium (IV) chloride as a key step.
- Takemoto, Yoshiji,Matsumoto, Teruyo,Ito, Yoshio,Terashima, Shiro
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p. 217 - 218
(2007/10/02)
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- Synthesis of Statine and Its Analogues
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Statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, and its analogues were prepared from 5,6-anhydro-3-deoxy-1,2-O-isopropylidene-D-glucofuranose.The key step is the stereospecific reaction of the epoxy sugar with the Grignard reagent.
- Yanagisawa, Hiroaki,Kanazaki, Takuro,Nishi, Takahide
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p. 687 - 690
(2007/10/02)
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- Synthesis of Diastereomerically and Enantiomerically Pure (3S,4S)-Statine from (R)-2,3-O-Isopropylideneglyceraldehyde
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Diastereomerically and enantiomerically pure (3S,4S)-statine (2), the non-proteinogenic amino acid of the protease inhibitor pepstatin (1), has been prepared from (R)-2,3-O-isopropylideneglyceraldehyde (4) in nine steps and 13percent overall yield.
- Mulzer, Johann,Buettelmann, Bernd,Muench, Winfried
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p. 445 - 448
(2007/10/02)
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- SYNTHESIS OF ASATINE AND ITS ANALOGUES BY HOMOGENEOUS ASYMMETRIC HYDROGENATION
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Diastereoselective hydrogenation of N-protected γ-amino β-keto esters catalyzed by BINAP-Ru(II) complexes provides an efficient entry to the statine series with high enantiomeric purities.
- Nishi, T.,Kitamura, M.,Ohkuma, T.,Noyori, R.
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p. 6327 - 6330
(2007/10/02)
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- A NEW FACILE DIASTEREOCONVERSION OF 2-AMINO ALCOHOLS INVOLVING A NOVEL CYCLOCARBAMATION
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A new practical method for diastereoconversion of 2-amino alcohols was performed by treatment on N-Cbz- derivatives with trifluoromethanesulfonic anhydride or thionyl chloride, followed by ring cleavage of the resulting oxazolidin-2-ones
- Kano, Shinzo,Yokomatsu, Tsutomu,Iwasawa, Haruo,Shibuya, Shiroshi
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p. 6331 - 6334
(2007/10/02)
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- Synthesis of all the stereoisomers of statine (4-amino-3-hydroxy-6-methylheptanoic acid). Inhibition of pepsin activity by N-carbobenzoxy-L-valyl-L-valyl-statine derived from the four stereoisomers.
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Synthesis of all four stereoisomers of the novel amino acid statine, 4-amino-3-hydroxy-6-methylheptanoic acid, found in pepstatin, a potent acid protease inhibitor, has been accomplished. Carbobenzoxy-L-valyl-L-valyl-statine tripeptides derived from all f
- Liu,W.-S. et al.
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p. 577 - 579
(2007/10/06)
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