118635-66-8Relevant articles and documents
Synthesis of Novel Potent Archazolids: Pharmacology of an Emerging Class of Anticancer Drugs
Scheeff, Stephan,Rivière, Solenne,Ruiz, Johal,Abdelrahman, Aliaa,Schulz-Fincke, Anna-Christina,K?se, Meryem,Tiburcy, Felix,Wieczorek, Helmut,Gütschow, Michael,Müller, Christa E.,Menche, Dirk
, p. 1684 - 1698 (2020)
Vacuolar type ATPase (V-ATPase) has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with archazolids, complex polyketide macrolides, which present the most potent V-ATPase inhibitors known to date. Herein, we report a biomimetic, one-step preparation of archazolid F, the most potent and least abundant archazolid, the design and synthesis of five novel, carefully selected archazolid analogues, and the biological evaluation of these antiproliferative agents, leading to the discovery of a very potent but profoundly simplified archazolid analogue. Furthermore, the first general biological profiling of the archazolids against a broad range of more than 100 therapeutically relevant targets is reported, leading to the discovery of novel and important targets. Finally, first pharmacokinetic data of these natural products are disclosed. All of these data are relevant in the further preclinical development of the archazolids as well as the evaluation of V-ATPases as a novel and powerful class of anticancer targets.
Modular Total Synthesis of iso-Archazolids and Archazologs
Dedenbach, Simon,Menche, Dirk,Rivière, Solenne,Ruiz, Johal,Scheeff, Stephan
, p. 10190 - 10223 (2021)
Full details on the design, development, and successful implementation of suitable synthetic strategies directed toward the total synthesis of iso-archazolids and archazologs are reported. Both a biomimetic and a multistep total synthesis of iso-archazolid B, the most potent and least abundant archazolid, are described. The bioinspired conversion from archazolid B was realized by a high-yielding 1,8-Diazabicyclo[5.4.0]undec-7-ene catalyzed one-step double-bond shift. A highly stereoselective total synthesis was accomplished in 25 steps, involving a sequence of highly stereoselective aldol reactions, an efficient aldol condensation to forge two elaborate fragments, and a challenging ring-closing metathesis macrocyclization with an unusual Stewart-Grubbs catalyst. These strategies proved to be generally useful and could be successfully implemented for the preparation of three novel iso-archazolids as well as five novel archazologs, lacking the thiazole side chain. A wide variety of further archazolids and archazologs may now be targeted for exploration of the promising anticancer potential of these polyketide macrolides.
Fischer Carbene Pentannulation with Alkynes Having Adjacent Carbonate or Acyloxy Groups: Synthesis of 3-Substituted 1-Indanones
Bhattacharyya, Shubhankar,Chavan, Vijay P.,Fernandes, Rodney A.,Gholap, Sachin P.,Saiyed, Akeel S.
, p. 3438 - 3443 (2020/04/20)
Various aryl Fischer carbenes reacted with alkynes having adjacent acyloxy or carbonate groups to regioselectively deliver 3-substituted 1-indanones. The acyloxy or carbonate group probably coordinates with the Cr metal to give a tetra-coordinated chromium complex forming a six-membered ring that retards CO insertion for ketene formation, which is required for benzannulation. Alternatively, the ortho position aryl ring attack results in pentannulation, providing regioselectively 3-substituted 1-indanones. The method is extended to the synthesis of the core structure of 3-epi-mutisianthol.
Anionic polycyclization entry to tricycles related to quassinoids and terpenoids: A stereocontrolled total synthesis of (+)-cassaine
Ravindar, Kontham,Caron, Pierre-Yves,Deslongchamps, Pierre
, p. 7979 - 7999 (2015/03/18)
A full account of our anionic polycyclization approach to access highly functionalized tricycles related to quassinoids and terpenoids from several optically active bicyclic enone systems and Nazarov reagents is presented. (+)-Carvone is the only chiral s
Oxidation of allylic and benzylic alcohols to aldehydes and carboxylic acids
K?nning, Daniel,Olbrisch, Tobias,Sypaseuth, Fanni D.,Tzschucke, C. Christoph,Christmann, Mathias
supporting information, p. 5014 - 5016 (2014/05/06)
An oxidation of allylic and benzylic alcohols to the corresponding carboxylic acids is effected by merging a Cu-catalyzed oxidation using O 2 as a terminal oxidant with a subsequent chlorite oxidation (Lindgren oxidation). The protocol was optimized to obtain pure products without chromatography or crystallization. Interception at the aldehyde stage allowed for Z/E-isomerization, thus rendering the oxidation stereoconvergent with respect to the configuration of the starting material.
Sequencing cross-metathesis and non-metathesis reactions to rapidly access building blocks for synthesis
Sirasani, Gopal,Paul, Tapas,Andrade, Rodrigo B.
experimental part, p. 2197 - 2205 (2011/04/22)
The olefin cross-metathesis reaction has been sequenced with four common organic transformations in a one- or two-pot manner to rapidly access useful building blocks. Those reactions are: (1) phosphorus-based olefination (e.g., Wittig and Horner-Wadsworth-Emmons); (2) hydride reduction; (3) Evans propionate aldol reaction; (4) Brown allyl- and Roush crotyl-boration. The products of these reactions include stereodefined 2,4-dienoates, trans allylic alcohols, syn-propionate aldols, and chiral non-racemic homoallylic alcohols, respectively. Many of these intermediates have been carried further to natural products, demonstrating the utility of the methodology.
Total synthesis of largazole
Ren, Qi,Dai, Lu,Zhang, Hui,Tan, Wenfei,Xu, Zhengshuang,Ye, Tao
body text, p. 2379 - 2383 (2009/05/27)
The stereocontrolled total synthesis of largazole was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction, thiazoline-thiazole formation, and macrolactamization by use of the Mukaiyama reagent. Georg Thieme Verlag Stuttgart.
One-pot sequential cross-metathesis/hydride reduction: highly stereoselective synthesis of primary (E)-allylic alcohols from terminal olefins
Paul, Tapas,Sirasani, Gopal,Andrade, Rodrigo B.
, p. 3363 - 3367 (2008/09/21)
Several di- and trisubstituted primary (E)-allylic alcohols have been prepared from the corresponding terminal olefins in a highly stereoselective manner (>20:1 E/Z) by sequencing olefin cross-metathesis (CM) with hydride reduction (DIBAL-H) in good yields utilizing only commercially available reagents in a one-pot fashion. The method is a reliable alternative to the direct CM of terminal olefins with allyl alcohol, which is not always stereoselective but rather highly substrate dependent.
Titanium tetrachloride-mediated enantioselective synthesis of trans β-lactones
Cardani, Silvia,De Toma, Carlo,Gennari, Cesare,Scolastico, Carlo
, p. 5557 - 5564 (2007/10/02)
Pharmacologically interesting trans β-lactones 11 and 16 were synthesized using a titanium tetrachloride-mediated enantioselective aldol reaction as the key synthetic step (see Scheme 2).
