37428-58-3Relevant academic research and scientific papers
Insights into the structure–activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety
Qian, Shan,Shah, Aashay K.,Head, Sarah A.,Liu, Jun O.,Jin, Zhendong
, p. 3411 - 3413 (2016)
Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure–activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2–C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4–C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity.
Synthesis of the C1-C12 Fragment of Calyculin C
Konstantinova, Olga V.,Koskinen, Ari M.P.
, p. 285 - 295 (2019/01/04)
Calyculins are a class of highly cytotoxic metabolites originally isolated from the marine sponge Discodermia calyx. To date, a total of twelve different calyculins (A-J) and calyculinamides (A, B and F) have been described, the most abundant (in D. calyx
Metathesis at an Implausible Site: A Formal Total Synthesis of Rhizoxin D
Karier, Pol,Ungeheuer, Felix,Ahlers, Andreas,Anderl, Felix,Wille, Christian,Fürstner, Alois
supporting information, p. 248 - 253 (2018/12/13)
The new approach to the anticancer agent rhizoxin D described herein does not cohere with the conventional logic of metathesis, according to which macrocycles are best closed at a disubstituted olefinic site; rather, the trisubstituted C11?C12 alkene flanked by an allylic -OH group served as the pivot point for synthesis. This motif was attained in good yield and excellent selectivity by a sequence of alkyne metathesis, trans-hydrostannation and cross coupling. Because the exact same substructure is prominently featured in numerous other natural products, the underpinning strategy, though unusual, might bear more general relevance.
Stereoselectivity of electrophile-promoted oxacyclizations of 1,4-dihydroxy-5-alkenes to 3-hydroxytetrahydropyrans Dedicated to Professor Paul A. Wender with heartiest congratulations on his receipt of the 2012 Tetrahedron Prize for Creativity in Organic
McDonald, Frank E.,Ishida, Kento,Hurtak, Jessica A.
, p. 7746 - 7758 (2013/08/23)
Stereoinduction from the allylic hydroxyl group of 1,4-dihydroxy-5-alkenes has been systematically explored with various alkene substitution patterns and electrophilic reagents. For formation of erythro-diastereomers of 2-substituted 3-hydroxytetrahydropy
Total synthesis of (-)-zampanolide and structure-activity relationship studies on (-)-dactylolide derivatives
Zurwerra, Didier,Glaus, Florian,Betschart, Leo,Schuster, Julia,Gertsch, Jürg,Ganci, Walter,Altmann, Karl-Heinz
supporting information, p. 16868 - 16883 (2013/03/14)
A new total synthesis of the marine macrolide (-)-zampanolide (1) and the structurally and stereochemically related non-natural levorotatory enantiomer of (+)-dactylolide (2), that is, ent-2, has been developed. The synthesis features a high-yielding, selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction to close the 20-membered macrolactone ring of 1 and ent-2. The β-keto phosphonate/aldehyde precursor for the ring-closure reaction was obtained by esterification of a ω-diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent-2. THP ring formation was accomplished through a segment coupling Prins-type cyclization. Employing the same overall strategy, 13-desmethylene-ent-2 as well as the monocyclic desTHP derivatives of 1 and ent-2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro with nM IC50 values, while ent-2, which lacks the diene-containing hemiaminal-linked side chain of 1, is 25- to 260-fold less active. 13-Desmethylene-ent-2 as well as the reduced versions of ent-2 and 13-desmethylene-ent-2 all showed similar cellular activity as ent-2 itself. The same activity level was attained by the monocyclic desTHP derivative of 1. Oxidation of the aldehyde functionality of ent-2 gave a carboxylic acid that was converted into the corresponding N-hexyl amide. The latter showed only μM antiproliferative activity, thus being several hundred-fold less potent than 1. It's the side chain that matters: The marine macrolide (-)-zampanolide (1) has been synthesized via (-)-dactylolide (ent-2), the non-natural enantiomer of the marine natural product (+)-dactylolide (2), employing a high-yielding intramolecular Horner-Wadsworth-Emmons reaction to close the macrolactone ring. While the hemiaminal-linked side chain in 1 is crucial for nanomolar antiproliferative activity, the methylene group and the aldehyde functionality in ent-2 are dispensable. A monocyclic destetrahydropyran derivative of 1 shows equal activity as ent-2. Copyright
The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments
Paterson, Ian,Anderson, Edward A.,Dalby, Stephen M.,Lim, Jong Ho,Maltas, Philip,Loiseleur, Olivier,Genovino, Julien,Moessner, Christian
supporting information; experimental part, p. 5861 - 5872 (2012/08/28)
Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.
New synthetic methodology for the construction of 7-substituted farnesyl diphosphate analogs
Placzek, Andrew T.,Gibbs, Richard A.
supporting information; experimental part, p. 3576 - 3579 (2011/09/14)
Through the use of a 1,2-metalate rearrangement, six 7-substituted farnesol analogs were generated in a concise manner. This new synthetic route allowed us to quickly prepare several diverse farnesyl diphosphate analogs with interesting biological activit
Total synthesis of peridinin and related C37-norcarotenoid butenolides
Vaz, Belen,Dominguez, Marta,Alvarez, Rosana,De Lera, Angel R.
, p. 1273 - 1290 (2007/10/03)
As an extension of our synthesis of symmetrical carotenoids, the preparation of the highly functionalized C37-norcarotenoid butenolide peridinin (1), its 6′-epi- and 11′Z stereoisomers has been completed. Featuring a central dihalogenated Csub
Total synthesis of paracentrone, C31-allenic opo-carotenoid
Murakami, Yusuke,Nakano, Masayuki,Shimofusa, Takuya,Furuichi, Noriyuki,Katsumura, Shigeo
, p. 1372 - 1374 (2007/10/03)
The stereocontrolled total synthesis of a C31-allenic apocarotenoid, paracentrone, was achieved by the convergent C20 + C11 = C31 strategy. The key elements of our synthesis were the Pd-catalyzed cross-coupling to stereoselectively construct the conjugated polyene backbone skeleton and the designed geometrical isomerization at the central double bond of the conjugated polyene chain. In addition, the terminal oxygenated cyclohexane ring having the allenic moiety was prepared by the highly diastereoselective Sharpless epoxidation under our own reaction conditions. The Royal Society of Chemistry 2005.
Intramolecular [4 + 2] cycloadditions of benzynes with conjugated enynes, arenynes, and dienes
Hayes, Martin E.,Shinokubo, Hiroshi,Danheiser, Rick L.
, p. 3917 - 3920 (2007/10/03)
(Chemical Equation Presented) Benzynes generated by the reaction of o-(trimethylsilyl)aryl triflates with TBAT participate in intramolecular [4 + 2] cycloadditions with conjugated enynes, arenynes, and dienes to furnish highly condensed polycyclic aromatic compounds.
