125975-53-3Relevant academic research and scientific papers
A Method for the Stereoselective Construction of the Hemiaminal Center in Zampanolides
Brütsch, Tobias M.,Berardozzi, Simone,Rothe, Marlene L.,Horcajo, Mariano Redondo,Diáz, José Fernando,Altmann, Karl-Heinz
, p. 8345 - 8348 (2020)
We have developed a new method for the stereoselective establishment of the N-acyl hemiaminal moiety in zampanolide-type structures that involves the reaction of (Z,E)-sorbamide (3) with BINAL-H and subsequent amide transfer from a putative aluminum carbo
Synthesis of solandelactone F, constanolactone A and an advanced intermediate towards solandelactone e from a common synthetic intermediate
Yalla, Raju,Raghavan, Sadagopan
, p. 4572 - 4592 (2019)
The stereoselective synthesis of solandelactone F, constanolactone A and an advanced intermediate towards solandelactone E, from a common synthetic intermediate, is disclosed. The propargylic sulfide stereocenter is created stereoselectively via carbon-carbon bond formation in the reaction of α-chloro sulfides with alkynylzinc reagents via 1,2-asymmetric induction by a β-siloxy group. The characteristic 1,4-diol motif of the natural products is introduced by a [2,3] sigmatropic rearrangement of an allylic sulfoxide or by the Mislow-Evans-Braverman rearrangement of a propargylic sulfoxide followed by stereoselective reduction of the ensuing α,β-unsaturated ketone. Unlike earlier reports, the C11/C9 carbinol center is created with excellent stereocontrol and derivatives of natural products differing at C14/C12 can be readily obtained. Catalytic asymmetric protocols and substrate-controlled asymmetric induction are utilized for the efficient introduction of the stereogenic centers.
Synthesis of the C10-C24-bis-spiroacetal core of 13-desmethyl spirolide C based on a sila-stetter-acetalization process
Labarre-Laine, Jessica,Perinan, Ignacio,Desvergnes, Valerie,Landais, Yannick
, p. 9336 - 9341 (2014)
Synthesis of the bis-spiroacetal core of 13-desmethyl spirolide C has been completed based on a sila-Stetter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in 7 and 11 steps, respectively, from (S) and (R)-a
Second-generation synthesis of (-)-viriditoxin
Grove, Charles I.,Fettinger, James C.,Shaw, Jared T.
scheme or table, p. 362 - 371 (2012/03/27)
Viriditoxin is a secondary metabolite isolated from Aspergillus viridinutans that has been shown to inhibit FtsZ, the bacterial homologue of eukaryotic tubulin. A streamlined, scalable, and highly diastereoselective synthesis of this complex natural product is described. Key advances include a more efficient synthesis of the requisite unsaturated pyranone, scalable assembly of the naphthopyranone monomer, and improved diastereoselectivity in the biaryl-coupling reaction. In addition, we disclose a serendipitous ruthenium-catalyzed anion dimerization resulting from trace metal left by an RCM reaction. Georg Thieme Verlag Stuttgart New York.
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
Total synthesis of decarestrictine i and botryolide B via RCM protocol
Radha Krishna, Palakodety,Rao, T. Jagannadha
scheme or table, p. 3130 - 3132 (2010/08/21)
A convergent stereoselective total synthesis of decarestrictine I (1) and botryolide B (1a) invoking a common synthetic strategy is reported. The key steps are: ring-closing metathesis of epoxy dienoic esters obtained through the Yamaguchi esterification
A concise stereoselective formal total synthesis of the cytotoxic macrolide (+)-Neopeltolide via Prins cyclization
Yadav, Jhillu Singh,Krishana, Gunda Gopala,Kumar, Satya Narayana
body text, p. 480 - 487 (2010/03/03)
A convergent and highly stereoselective formal total synthesis of the naturally occurring, cytotoxic 14-membered macrolide neopeltolide has been achieved via two Prins cyclizations.
Synthesis of (-)-dactylolide and 13-desmethylene-(-)-dactylolide and their effects on tubulin
Zurwerra, Didier,Gertsch, Juerg,Altmann, Karl-Heinz
supporting information; experimental part, p. 2302 - 2305 (2010/08/05)
An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (-)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the sub-micromolar range and induce the polymerization of tubulin in vitro.
A [3 + 3] annelation approach to (+)-rhopaloic acid B
Brioche, Julien C. R.,Goodenough, Katharine M.,Whatrup, David J.,Harrity, Joseph P. A.
, p. 3941 - 3943 (2008/02/11)
A general and enantiospecific [3 + 3] reaction toward functionalized pyrans is reported that has been employed in the first enantioselective synthesis of (+)-rhopaloic acid B.
Synthesis of the anti-Helicobacter pylori agent (+)-spirolaxine methyl ether and the unnatural (2″S)-diastereomer
Robinson, James E.,Brimble, Margaret A.
, p. 2572 - 2582 (2008/03/12)
The first enantioselective synthesis of the anti-Heliocbacter pylori agent (+)-spirolaxine methyl ether 2b has been carried out in a convergent fashion establishing that the absolute stereochemistry of the natural product is in fact (3R, 2″R, 5″R, 7″R) after initial synthesis of the unnatural (2″S)-diastereomer 2a. The key step in the synthesis of (+)-spirolaxine methyl ether 2b involved a heterocycle-activated Julia-Kocienski olefination between benzothiazole-based spiroacetal sulfone 4b and phthalide aldehyde 3a. (2″R, 5″S, 7″S)-Spiroacetal sulfone 4b was prepared via cyclisation of protected dihydroxyketone 6b, which in turn was derived from the coupling of the acetylide derived from (R)-acetylene 24b with aldehyde 3a. Phthalide aldehyde 3a was prepared via intramolecular acylation of bromocarbamate 15, which was available via titanium tetrafluoride-(+)-BINOL- mediated allylation of 3,5-dimethoxybenzaldehyde 13. Union of the sulfone 4b and aldehyde 3a fragments successfully completed the enantioselective synthesis of (+)-spirolaxine methyl ether 2b. The synthesis of the unnatural (3R, 2″S, 5″R, 7″R)-diastereomer of spirolaxine methyl ether 2a was also undertaken in a similar manner by union of phthalide aldehyde 3a with (2″S, 5″S, 7″S)-spiroacetal sulfone 4a derived from (S)-acetylene 24a. The Royal Society of Chemistry.
