152899-13-3Relevant articles and documents
Understanding Programming of Fungal Iterative Polyketide Synthases: The Biochemical Basis for Regioselectivity by the Methyltransferase Domain in the Lovastatin Megasynthase
Cacho, Ralph A.,Thuss, Justin,Xu, Wei,Sanichar, Randy,Gao, Zhizeng,Nguyen, Allison,Vederas, John C.,Tang, Yi
, p. 15688 - 15691 (2015)
Highly reducing polyketide synthases (HR-PKSs) from fungi synthesize complex natural products using a single set of domains in a highly programmed, iterative fashion. The most enigmatic feature of HR-PKSs is how tailoring domains function selectively during different iterations of chain elongation to afford structural diversity. Using the lovastatin nonaketide synthase LovB as a model system and a variety of acyl substrates, we characterized the substrate specificity of the LovB methyltransferase (MT) domain. We showed that, while the MT domain displays methylation activity toward different β-ketoacyl groups, it is exceptionally selective toward its naturally programmed β-keto-dienyltetraketide substrate with respect to both chain length and functionalization. Accompanying characterization of the ketoreductase (KR) domain displays broader substrate specificity toward different β-ketoacyl groups. Our studies indicate that selective modifications by tailoring domains, such as the MTs, are achieved by higher kinetic efficiency on a particular substrate relative to the rate of transformation by other competing domains.
Synthesis of Rhamnolipid Derivatives Containing Ester Isosteres
Lowary, Todd L.,Wang, Lei
, p. 9633 - 9637 (2020)
Rhamnolipids are biosurfactants with many applications, arising from their inherent biological activity and their potential as bioremediation agents. Herein, we report the synthesis of four rhamnolipid derivatives in which the ester linkage connecting the
Structural Requirements of HDAC Inhibitors: SAHA Analogues Modified at the C2 Position Display HDAC6/8 Selectivity
Negmeldin, Ahmed T.,Padige, Geetha,Bieliauskas, Anton V.,Pflum, Mary Kay H.
supporting information, p. 281 - 286 (2017/03/17)
Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as antica
Volatile methyl esters of medium chain length from the bacterium Chitinophaga Fx7914
Nawrath, Thorben,Gerth, Klaus,Mueller, Rolf,Schulz, Stefan
experimental part, p. 2228 - 2253 (2011/05/17)
The analysis of the volatiles released by the novel bacterial isolate Chitinophaga Fx7914 revealed the presence of ca. 200 compounds including different methyl esters. These esters comprise monomethyl- and dimethyl-branched, saturated, and unsaturated fatty acid methyl esters that have not been described as bacterial volatiles before. More than 30 esters of medium C-chain length were identified, which belong to five main classes, methyl (S)-2-methylalkanoates (class A), methyl (S)-2,(ω-1)-dimethylalkanoates (class B), methyl 2,(ω-2)-dimethylalkanoates (class C), methyl (E)-2-methylalk-2-enoates (class D), and methyl (E)-2,(ω-1)-dimethylalk-2- enoates (class E). The structures of the compounds were verified by GC/MS analysis and synthesis of the target compounds as methyl (S)-2-methyloctanoate (28), methyl (S)-2,7-dimethyloctanoate ((S)-43), methyl 2,6-dimethyloctanoate (49), methyl (E)-2-methylnon-2-enoate (20a), and methyl (E)-2,7-dimethyloct-2- enoate (41a). Furthermore, the natural saturated 2-methyl-branched methyl esters showed (S)-configuration as confirmed by GC/MS experiments using chiral phases. Additionally, the biosynthetic pathway leading to the methyl esters was investigated by feeding experiments with labeled precursors. The Me group at C(2) is introduced by propanoate incorporation, while the methyl ester is formed from the respective carboxylic acid by a methyltransferase using S-adenosylmethionine (SAM).
Total synthesis of emericellamides A and B
Li, Shuo,Liang, Shuo,Tan, Wenfei,Xu, Zhengshuang,Ye, Tao
experimental part, p. 2695 - 2702 (2009/06/28)
The total synthesis of emericellamides A and B is reported. A convergent, flexible strategy employing peptide chemistry, asymmetric alkylations, and culminating in macrolactamization is described. The previously reported structure of both compounds is confirmed.
Isolation and total synthesis of gymnastatin N, a POLO-like kinase 1 active constituent from the fungus Arachniotus punctatus
Phoon, Chee Wee,Somanadhan, Brinda,Heng, Sabrina Cher Hui,Ngo, Anna,Ng, Siew Bee,Butler, Mark S.,Buss, Antony D.,Sim, Mui Mui
, p. 11619 - 11628 (2007/10/03)
A high throughput screen against POLO-like kinase 1 (Plk1), an anti-cancer target, identified an active extract from the fungus Arachniotus punctatus. Bioassay guided fractionation led to the isolation of the new natural product, gymnastatin N (1) and the known compound aranorosinol A (2) with IC50 values of 13 and 118 μM, respectively. A 12′-hydroxy analog of gymnastatin N, 3, was also isolated as a minor component. Gymnastatin N (1) was found to be a 52:48 mixture of (1S,6′R) and (1R,6′R) diastereomers, by synthesis of the four possible diastereomers and comparison of the optical rotation and chiral HPLC profile of each diastereoisomer with the natural product. Analogues of 1 were synthesized and evaluated against the Plk1 assay and these SAR studies suggested that the diene and free carboxylic acid moieties might be responsible for its bioactivity. Graphical Abstract.
An efficient strategy for the synthesis of chiral liquid crystals using Evans' methodology
Merlo, Aloir A.,Fernandes, Mirele S.
, p. 1167 - 1178 (2007/10/03)
The synthesis of liquid crystal compound 2 was achieved using Evans' methodology. The strategy was based on three key synthetic reactions: alkylation of chiral amide enolates, Mitsunobu and, finally, esterification. The final compound presents a stable smectic A phase.
Matrix metalloproteinase inhibitors: A structure-activity study
Levy, Daniel E.,Lapierre, France,Liang, Weisheng,Ye, Wenqing,Lange, Christopher W.,Li, Xiaoyuan,Grobelny, Damian,Casabonne, Marie,Tyrrell, David,Holme, Kevin,Nadzan, Alex,Galardy, Richard E.
, p. 199 - 223 (2007/10/03)
Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
Inhibition of matrix metalloproteinases: An examination of the S1' pocket
Miller, Andrew,Askew, Marion,Beckett, R. Paul,Bellamy, Claire L.,Bone, Elisabeth A.,Coates, Rachael E.,Davidson, Alan H.,Drummond, Alan H.,Huxley, Philip,Martin, Fionna M.,Saroglou, Lydia,Thompson, Alison J.,Van Dijk, Sonja E.,Whittaker, Mark
, p. 193 - 198 (2007/10/03)
Peptidomimetic carboxylate- and hydroxamate-based inhibitors of matrix metalloproteinases containing extended P1' groups have been prepared. Potent inhibition and good selectivity for MMP-2 has been observed for the compounds produced.
The total synthesis of the diepoxycyclohexanone antibiotic aranorosin and novel synthetic analogues
McKillop, Alexander,McLaren, Lee,Taylor, Richard J. K.,Watson, Robert J.,Lewis, Norman J.
, p. 1385 - 1393 (2007/10/03)
A short synthesis of the novel antibiotic aranorosin in chiral form is described which employs (i) a novel hypervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative and (ii) a stereocontrolled cis-bisepoxidation in the key steps. A similar procedure was employed to prepare 6′-epiaranorosin, and hence establish the stereochemistry of the natural compound, and to prepare novel aranorosin analogues. An organometallic route is described which gives desamidoaranorosin.
