112897-09-3Relevant articles and documents
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
supporting information, p. 8345 - 8348 (2020/11/03)
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
Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle 23 Has Negligible Impact on Its Biological Profile and Potency
Zhao, Xiguang,Kedei, Noemi,Michalowski, Alexandra,Lewin, Nancy E.,Keck, Gary E.,Blumberg, Peter M.
, p. 1049 - 1059 (2018/05/31)
Important strides are being made in understanding the effects of structural features of bryostatin 1, a candidate therapeutic agent for cancer and dementia, in conferring its potency toward protein kinase C and the unique spectrum of biological responses that it induces. A critical pharmacophoric element in bryostatin 1 is the secondary hydroxy group at the C26 position, with a corresponding primary hydroxy group playing an analogous role in binding of phorbol esters to protein kinase C. Herein, we describe the synthesis of a bryostatin homologue in which the C26 hydroxy group is primary, as it is in the phorbol esters, and show that its biological activity is almost indistinguishable from that of the corresponding compound with a secondary hydroxy group.
Remarkable Influence of Cobalt Catalysis on Epoxide Ring-Opening with Sulfoxonium Ylides
Jamieson, Megan L.,Brant, Nicola Z.,Brimble, Margaret A.,Furkert, Daniel P.
, p. 3952 - 3956 (2017/08/29)
Cobalt demonstrates a remarkable ability to catalytically divert the course of epoxide to oxetane ring expansion via reaction with a sulfoxonium ylide. An expanded survey of transition-metal catalysts has confirmed that cobalt salts uniquely instead deliv
Substitution dependent stereoselective construction of bicyclic lactones and its application to the total synthesis of pyranopyran, tetraketide and polyrhacitide A
Subba Reddy,Biradar, Dhanraj O.,Vikram Reddy,Yadav,Singarapu, Kiran Kumar,Sridhar
supporting information, p. 8832 - 8837 (2016/10/03)
A novel bicyclization strategy has been developed for the stereoselective synthesis of bicyclic lactones, i.e. 7-aryl or alkyl-2,6-dioxabicyclo[3.3.1]nonan-3-ones through a domino cyclization of (R)-3-hydroxyhex-5-enoic acid with an aldehyde in the presen
Total Synthesis of Δ12-Prostaglandin J3: Evolution of Synthetic Strategies to a Streamlined Process
Nicolaou,Pulukuri, Kiran Kumar,Yu, Ruocheng,Rigol, Stephan,Heretsch, Philipp,Grove, Charles I.,Hale, Christopher R. H.,ElMarrouni, Abdelatif
supporting information, p. 8559 - 8570 (2016/07/11)
The total synthesis of Δ12-prostaglandin J3(Δ12-PGJ3, 1), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross-conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14, whose lone stereocenters were generated by an asymmetric Tsuji–Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent-governed regioselectivity pattern for the Rh-catalyzed C?H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14, exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57, and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large-scale production of Δ12-PGJ3and designed analogues for further biological and pharmacological studies.
Divergent reactivity via cobalt catalysis: An epoxide olefination
Jamieson, Megan L.,Hume, Paul A.,Furkert, Daniel P.,Brimble, Margaret A.
supporting information, p. 468 - 471 (2016/02/18)
Cobalt salts exert an unexpected and profound influence on the reactivity of epoxides with dimethylsulfoxonium methylide. In the presence of a cobalt catalyst, conditions for epoxide to an oxetane ring expansion instead deliver homoallylic alcohol products, corresponding to a two-carbon epoxide homologation/ring-opening tandem process. The observed reactivity change appears to be specifically due to cobalt salts and is broadly applicable to a variety of epoxides, retaining the initial stereochemistry. This transformation also provides operationally simple access to enantiopure homoallylic alcohols from chiral epoxides without use of organometallic reagents. Tandem epoxidation-homologation of aldehydes in a single step is also demonstrated.
Synthetic approach to wortmannilactone C
Brandt, Damien,Dittoo, Aurlia,Bellosta, Vronique,Cossy, Janine
supporting information, p. 816 - 819 (2015/03/18)
A diastereomer of wortmannilactone C has been synthesized according to a convergent and versatile strategy from tert-butyl 3-hydroxypropanoate and ethyl (R)-3-hydroxybutanoate. The key steps are a Liebeskind cross-coupling and a Horner-Wadsworth-Emmons (HWE) reaction to construct the macrolactone. The stereogenic centers at C9, C11, and C21 were controlled by enantioselective allyltitanations, and the C19 stereocenter was controlled by using a Noyori reduction of an acetylenic ketone.
Total synthesis of the marine toxin phorboxazole A using palladium(ii)-mediated intramolecular alkoxycarbonylation for tetrahydropyran synthesis
Kuntiyong, Punlop,Lee, Tae Hee,Kranemann, Christian L.,White, James D.
supporting information, p. 7884 - 7899 (2013/07/05)
The potent antitumor agent phorboxazole A was synthesized from six subunits comprising C1-C2 (115), C3-C8 (98), C9-C19 (74), C20-C32 (52), C33-C41 (84) and C42-C46 (85). Tetrahydropyrans B and C containing cis-2,6-disubstitution were fabricated via palladium(ii)-mediated intramolecular alkoxycarbonylation which, in the case of tetrahydropyran C, was carried out with catalytic palladium(ii) and p-benzoquinone as the stoichiometric re-oxidant. Tetrahydropyran D was obtained by a stereoselective tin(iv)-catalyzed coupling of a C9 aldehyde with an allylsilane, and the C19-C20 connection was made using a completely stereoselective Wittig-Schlosser (E) olefination. Coupling of the oxazole C32 methyl substituent with the intact C33-C46 δ-lactone 3 was accompanied by elimination of the vinyl bromide to a terminal alkyne, but the C32-C33 linkage was implemented successfully with 83 and C33-C41 lactone 84. The C42-C46 segment of the side chain was then appended via Julia-Kocienski olefination. The macrolide portion of phorboxazole A was completed by means of an Ando-Still-Gennari intramolecular (Z)-selective olefination at C2-C3 which required placement of a (dimethoxyphosphinyl)acetate moiety at C24. Final deprotection led to phorboxazole A via a route in which the longest linear sequence is 37 steps and the overall yield is 0.36%.
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
