169105-67-3Relevant academic research and scientific papers
Diverted total synthesis of the baulamycins and analogues reveals an alternate mechanism of action
Steele, Andrew D.,Ernouf, Guillaume,Lee, Young Eun,Wuest, William M.
supporting information, p. 1126 - 1129 (2018/02/23)
The baulamycins were identified as in vitro siderophore biosynthesis inhibitors. Diverted total synthesis was used to construct the natural products and eight strategic analogues, three of which had improved inhibitory activity. Biological testing then revealed that membrane damage is the predominant mode of action in Staphylococcus aureus cells.
Highly stereoselective total synthesis of (+)-9-epi-Dictyostatin and (-)-12,13-Bis-epi-dictyostatin
Zanato, Chiara,Pignataro, Luca,Ambrosi, Andrea,Hao, Zhongyan,Trigili, Chiara,Diaz, Jose Fernando,Barasoain, Isabel,Gennari, Cesare
, p. 2643 - 2661 (2011/06/25)
The total syntheses of (+)-9-epi-dictyostatin (1a) and (-)-12,13-bis-epi- dictyostatin (1b), diastereomers of the antimitotic marine sponge-derived macrolide (-)-dictyostatin (1), were achieved by creating 11 stereogenic centers and 4stereogenic double bonds with a high level of stereocontrol. The yield for the 29-step longest linear sequence from Roche ester was 1.53 and 1.52%, respectively. The final key steps to these unnatural products were the addition of vinylzincates C10-C26 to aldehyde C1-C9 (leading surprisingly to complete stereoselectivity for the 9R-configuration in 28a and for the 9S-configuration in 12,13-bis-epimeric 28b), followed by Yamaguchi macrolactonization and global deprotection. (-)-12,13-Bis-epi-dictyostatin (1b) displayed a dramatic decrease of cytotoxicity and of the affinity toward the paclitaxel binding site of microtubules. Eleven stereogenic centers and fourstereogenic double bonds were obtained with a high level of stereocontrol in the total synthesis of (+)-9-epi-dictyostatin and(-)-12,13-bis-epi-dictyostatin, diastereomers of the antimitotic marine sponge-derived macrolide (-)-dictyostatin.
Mechanism and stereospecificity of a fully saturating polyketide synthase module: Nanchangmycin synthase module 2 and its dehydratase domain
Guo, Xun,Liu, Tiangang,Valenzano, Chiara R.,Deng, Zixin,Cane, David E.
, p. 14694 - 14696 (2011/01/07)
Recombinant nanchangmycin synthase module 2 (NANS module 2), with the thioesterase domain from the 6-deoxyerythronolide B synthase (DEBS TE) appended to the C-terminus, was cloned and expressed in Escherichia coli. Incubation of NANS module 2+TE with (±)-2-methyl-3-keto-butyryl-N-acetylcysteamine thioester (1), the SNAC analog of the natural ACP-bound substrate, with methylmalonyl-CoA (MM-CoA) in the absence of NADPH gave 3,5,6-trimethyl-4- hydroxypyrone (2), identified by direct comparison with synthetic 2 by radio-TLC-phosphorimaging and LC-ESI(+)-MS-MS. The reaction showed k cat 0.5 ± 0.1 min-1 and Km(1) 19 ± 5 mM at 0.5 mM MM-CoA and kcat(app) 0.26 ± 0.02 min-1 and Km(MM-CoA) 0.11 ± 0.02 mM at 8 mM 1. Incubation in the presence of NADPH generated the fully saturated triketide chain elongation product as a 5:3 mixture of (2S,4R)-2,4-dimethyl-5-ketohexanoic acid (3a) and the diastereomeric (2S,4S)-3b. The structure and stereochemistry of each product was established by comparison with synthetic 3a and 3b by a combination of radio-TLC-phosphorimaging and LC-ESI(-)-MS-MS, as well as chiral capillary GC-MS analysis of the corresponding methyl esters 3a-Me and 3b-Me. The recombinant dehydratase domain from NANS module 2, NANS DH2, was shown to catalyze the formation of an (E)-double bond by syn-dehydration of the ACP-bound substrate anti-(2R,3R,4S,5R)-2,4-dimethyl-3,5-dihydroxyheptanoyl-ACP6 (4), generated in situ by incubation of (2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][AT6] didomain and ACP6 from DEBS module 6 along with the ketoreductase from the tylactone synthase module 1 (TYLS KR1). These results also indirectly establish the stereochemistry of the reactions catalyzed by the KR and enoylreductase (ER) domains of NANS module 2.
Total Synthesis of rapamycin
Ley, Steven V.,Tackett, Miles N.,Maddess, Matthew L.,Anderson, James C.,Brennan, Paul E.,Cappi, Michael W.,Heer, Jag P.,Helgen, Celine,Kori, Masakuni,Kouklovsky, Cyrille,Marsden, Stephen P.,Norman, Joanne,Osborn, David P.,Palomero, Maria A.,Pavey, John B. J.,Pinel, Catherine,Robinson, Lesley A.,Schnaubelt, Juergen,Scott, James S.,Spilling, Christopher D.,Watanabe, Hidenori,Wesson, Kieron E.,Willis, Michael C.
supporting information; experimental part, p. 2874 - 2914 (2009/12/25)
For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.
A highly stereoselective synthesis of the C10-C23 fragment of (-)-dictyostatin
Monti, Chiara,Sharon, Ofer,Gennari, Cesare
, p. 4271 - 4273 (2008/03/27)
A highly stereoselective synthesis of the C10-C23 fragment of (-)-dictyostatin has been achieved using a Carreira alkynylation and a Marshall-Tamaru allenylzinc addition as key steps. The Royal Society of Chemistry.
Application of the Doetz reaction to construction of a major portion of the ansa macrocycle (-)-kendomycin
White, James D.,Smits, Helmars
, p. 235 - 238 (2007/10/03)
(Chemical Equation Presented) A Doetz reaction employing a terminal alkyne and a Fischer-type alkenylchromium carbenoid led to a pentasubstituted benzene from which a major portion of the Streptomyces metabolite (-)-kendomycin was synthesized.
Synthetic studies on borrelidin: enantioselective synthesis of the C1-C12 fragment.
Vong, Binh G,Abraham, Sunny,Xiang, Alan X,Theodorakis, Emmanuel A
, p. 1617 - 1620 (2007/10/03)
[structure: see text] An efficient, enantioselective synthesis of the C1-C12 fragment 2 of borrelidin is presented. Construction of the "skipped" polymethylene chain of 2 was accomplished by iteration of Myers' alkylation, while formation of the C3 stereocenter was achieved by Roush's asymmetric allylboration methodology.
Synthesis of (+)-siphonarienone: Asymmetric alkylation using a chiral benzopyrano-isoxazolidine auxiliary
Abiko, Atsushi,Masamune, Satoru
, p. 1081 - 1084 (2007/10/03)
Asymmetric alkylation of the potassium enolates derived from N-propionyl benzopyrano[4,3-c]-isoxazolidine derivatives with chiral alkyl triflates proceeded smoothly with high diastereoselectivity. The stereochemistry of the newly formed stereogenic center was fully controlled by the facial selectivity of the enolate according to the rule of double asymmetric synthesis. The application of this methodology led to the first synthesis of (+)-siphonarienone, a marine polypropionate natural product.
