- Synthesis of the Bycroft-Gowland structure of micrococcin P1
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(formula presented) We describe the chemical synthesis of the accepted structure of micrococcin P1, a member of the thiostrepton group of antibiotics, and we show that this architecture does not correspond to that of the natural product. Methods developed during the present study should greatly facilitate ongoing efforts centering on the determination of the actual structure of microccin P1, in addition to being applicable to the synthesis of more complex thiostrepton congeners.
- Ciufolini, Marco A.,Shen, Yong-Chun
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- Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine
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Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.
- Ezawa, Tetsuya,Kawashima, Yuya,Noguchi, Takuya,Jung, Seunghee,Imai, Nobuyuki
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p. 1690 - 1699
(2017/11/14)
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- RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles
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The established cytotoxic agent RITA contains a thiophene-furan-thiophene backbone and two terminal alcohol groups. Herein we investigate the effect of using thiazoles as the backbone in RITA-like molecules and modifying the terminal groups of these trithiazoles, thereby generating 41 unique structures. Incorporating side chains with varied steric bulk allowed us to investigate how size and a stereocenter impacted biological activity. Subjecting compounds to growth inhibition assays on HCT-116 cells showed that the most potent compounds 7d, 7e, and 7h had GI50 values of 4.4, 4.4, and 3.4 μM, respectively, versus RITA (GI50 of 800 nM). Analysis of these compounds in apoptosis assays proved that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated that it acts via a different mechanism of action to that of RITA. RITA suppressed Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an alternative mechanism independent of p53.
- Pietkiewicz, Adrian L.,Zhang, Yuqi,Rahimi, Marwa N.,Stramandinoli, Michael,Teusner, Matthew,McAlpine, Shelli R.
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supporting information
p. 401 - 406
(2017/04/21)
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- Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation
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The preparation of peptide fragments containing dehydrovaline and dehydroisoleucine moieties present in the antibiotic myxovalargin is reported. Peptide formation is based on a copper-mediated C-N cross-coupling protocol between an acyl amide and a peptidic vinyl iodide. The presence of a neighboring arginine in the vinyl iodide posed a challenge with respect to the choice of the protecting group and the reaction conditions. It was found that ornithine - a suitable precursor - is better suited than arginine for achieving good yields for the C-N cross-coupling reaction. The optimized conditions were utilized for the synthesis of peptides 32, 33, 39 and 40 containing a neighboring ornithine as well as for the tripeptide 44 containing dehydroisoleucine with the correct stereochemistry.
- Gille, Franziska,Kirschning, Andreas
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supporting information
p. 564 - 570
(2016/04/08)
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- Total synthesis and complete structural assignment of Yaku'amide A
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Here we report the first total synthesis and the complete stereochemical assignment of yaku'amide A. Yaku'amide A (1) was isolated from a sponge Ceratopsion sp. as an extremely potent cytotoxin. Its structure was determined except for the C4-stereochemist
- Kuranaga, Takefumi,Sesoko, Yusuke,Sakata, Komei,Maeda, Naoya,Hayata, Atsushi,Inoue, Masayuki
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supporting information
p. 5467 - 5474
(2013/05/22)
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- 2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors
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A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo γ-secretase activity were identified and described.
- Parker, Michael F.,Barten, Donna M.,Bergstrom, Carl P.,Bronson, Joanne J.,Corsa, Jason A.,Dee, Michael F.,Gai, Yonghua,Guss, Valerie L.,Higgins, Mendi A.,Keavy, Daniel J.,Loo, Alice,Mate, Robert A.,Marcin, Larry R.,McElhone, Katharine E.,Polson, Craig T.,Roberts, Susan B.,MacOr, John E.
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p. 6828 - 6831,4
(2020/09/02)
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- Synthesis of the thiazole-thiazoline fragment of largazole analogues
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The thiazole - thiazoline fragment of the marine natural product largazole, a potent histone deacetylase 1 inhibitor, has been synthesized in five steps. The methodology provides rapid access to thiazole-4-carbonitrile, thiazole-4-carbimidate, thiazole -
- Diness, Frederik,Nielsen, Daniel S.,Fairlie, David P.
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experimental part
p. 9845 - 9851
(2012/01/02)
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- The preparation of optically active α-amino 4H-[1,2,4]oxadiazol-5-ones from optically active α-amino acids
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Optically active α-amino 4H-[1,2,4]oxadiazol-5-ones (oxadiazolones) were prepared from optically active α-amino acids in five synthetic steps. The oxadiazolone moiety serves as a bioisosteric replacement for the carboxylic acid. Incorporation of an α-amino oxadiazolone into a representative dipeptide mimic is described.
- Mangette, John E.,Johnson, Matthew R.,Le, Van-Duc,Shenoy, Rajesh A.,Roark, Howard,Stier, Michael,Belliotti, Thomas,Capiris, Thomas,Guzzo, Peter R.
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experimental part
p. 9536 - 9541
(2009/12/28)
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- Substituted benzofused heterocycles
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The present invention relates to the compounds of Formula I, their preparation and pharmaceutical compositions comprising them. The compounds and pharmaceutical compositions are useful, for example, for the treatment and prevention of obesity, obesity-related disorders and eating disorders.
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Page/Page column 39
(2008/06/13)
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- COMPOUNDS, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.
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Page/Page column 84
(2008/06/13)
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- Total synthesis of dendroamide A, a novel cyclic peptide that reverses multiple drug resistance
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Dendroamide A (1) was isolated from a blue-green alga on the basis of its ability to reverse drug resistance in tumor cells that overexpress either of the transport proteins, P-glycoprotein or MRP1. Because of this activity, methods for the synthesis of analogues of this oxazole- and thiazole-containing cyclic peptide have been developed; and the total synthesis of 1 has been completed. Highlights of the synthetic strategy are as follows: (1) a dicyclohexylcarbodiimide coupling of D-Ala and L-Thr, followed by reaction with Burgess reagent and DBU-assisted oxidation to form D-Alaoxazole; (2) formation of D-Val-thiazole and D-Ala-thiazole via modified Hantzsch reactions; and (3) use of molecular modeling to select the preferred precursor for the final cyclization of the peptide analogue. Synthetic 1 demonstrated spectral properties identical to those of the natural product and reversed P-glycoprotein-mediated drug resistance more effectively than MRP1-mediated resistance. Certain of the synthetic precursors had biological activity, indicating that cell permeability and peptide cyclization are necessary for optimal activity. Thus, the structure and the biological activities of the natural product are confirmed, and methods for the synthesis of analogues for further structure-activity explorations are defined.
- Xia,Smith
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p. 3459 - 3466
(2007/10/03)
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- Convenient Syntheses of Thiazoles Incorporated with α-Dehydroamino Acid and Dehydropeptide Structures
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The convenient syntheses of various thiazole α-dehydroamino acids, thiazole valine ethyl ester, and their dehydrodi- and tripeptides, which are important moieties and segment of micrococcin P1 and noshiheptide, macrocyclic peptide antibiotics,
- Nakamura, Yutaka,Shin, Chung-gi,Umemura, Kazuyuki,Yoshimura, Juji
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p. 1005 - 1008
(2007/10/02)
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- Synthetic studies towards cyclic peptides. Concise synthesis of thiazoline and thiazole containing amino acids
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Concise and efficient syntheses of optically pure thiazoline and thiazole containing amino acids of the constitution (26) and (27), based on simple condensation reactions between cysteine esters and N-protected imino ethers (22) and (25) derived from chir
- North, Michael,Pattenden, Gerald
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p. 8267 - 8290
(2007/12/18)
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