128461-65-4Relevant academic research and scientific papers
Synthesis of tetrahydrofurans from protected β-hydroxyaldehydes: Optimization of the alcohol protecting group
Angle, Steven R.,Bernier, Daniel S.,El-Said, Nahla A.,Jones, Darin E.,Shaw, Stephanie Z.
, p. 3919 - 3922 (1998)
As part of an effort to generalize the synthesis of substituted tetrahydrofurans from protected β-hydroxy aldehydes, a series of common alcohol protecting groups was screened for compatibility with the methodology. Employing a β-(triisopropylsilyloxy)alde
Synthesis of a simplified triazole analogue of pateamine A
Hemi Cumming,Brown, Sarah L.,Tao, Xu,Cuyamendous, Claire,Field, Jessica J.,Miller, John H.,Harvey, Joanne E.,Teesdale-Spittle, Paul H.
, p. 5117 - 5127 (2016)
Pateamine A is a naturally occurring metabolite extracted from the marine sponge Mycale hentscheli. It exhibits potent cytotoxicity towards cancer cell lines and has been shown to target protein translation initiation via inhibition of the function of euk
Stereoselective synthesis of (-)-pinidinone
Shankaraiah, Gundeti,Vijaya Kumar, Tiruvayamudi,Venkateswara Reddy, Guvvala,Madhusudana Rao, Janaswamy,Suresh Babu, Katragadda
, p. 990 - 996 (2013)
A simple and efficient stereoselective linear approach to the total synthesis of (-)-pinidinone has been accomplished starting from propane-1,3-diol, and employing Maruoka asymmetric allylation and Grubbs' olefin cross-metathesis as the key steps. Copyright
Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation
Choi, Sei-hyun,Franklin, Joseph Livy,Huang, Teng-Yi,Hung, Shang-Cheng,Jeon, Byung-sun,Kim, Namho,Liu, Hung-wen,Ruszczycky, Mark W.
supporting information, (2021/11/30)
Biosynthesis of spinosyn A in Saccharopolyspora spinosa involves a 1,4-dehydration followed by an intramolecular [4 + 2]-cycloaddition catalyzed by SpnM and SpnF, respectively. The cycloaddition also takes place in the absence of SpnF leading to questions
Modular Total Synthesis of iso-Archazolids and Archazologs
Dedenbach, Simon,Menche, Dirk,Rivière, Solenne,Ruiz, Johal,Scheeff, Stephan
, p. 10190 - 10223 (2021/08/16)
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.
Total Synthesis and Structure Revision of Halioxepine
Poock, Caroline,Kalesse, Markus
supporting information, p. 1615 - 1619 (2020/12/23)
The first total synthesis of halioxepine is accomplished using a 1,4-addition for constructing the quaternary center at C10 and a halo etherification for the generation of the tertiary ether at C7. The correct structure of halioxepine was determined by assembling different enantiomeric building blocks and by changing the relative configuration between C10 and C15.
BIOCATALYTIC SYNTHESIS OF CRYPTOPHYCIN ANTICANCER AGENTS
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Paragraph 0018; 0104, (2021/04/02)
The disclosure provides cryptophycin intermediates, cryptophycin analogs, and cryptophycin chimeric molecules useful in treating cancer, as well as methods of producing these compounds and methods of treating cancer.
Dictating Thermodynamic Control through Tethering: Applications to Stereoselective Bis-Spiroketal Synthesis
Asari, Austin H.,Floreancig, Paul E.
supporting information, p. 6622 - 6626 (2020/03/04)
Approaches to stereocontrol that invoke thermodynamic control fail when two or more potential products are energetically similar, but rational structural perturbations can be employed to break the energetic degeneracy and provide selective transformations. This manuscript illustrates that tethering is an effective approach for the stereoselective construction of bis-spiroketals with thermodynamically similar stereoisomers, providing a new approach to set remote stereocenters and prepare complex structures that have not previously been accessed stereoselectively.
Total synthesis of the actinoallolides and a designed photoaffinity probe for target identification
Anketell, Matthew J.,Paterson, Ian,Sharrock, Theodore M.
supporting information, p. 8109 - 8118 (2020/11/03)
The actinoallolides are a family of polyketide natural products isolated from the bacterium Actinoallomurus fulvus. They show potent biological activity against trypanosomes, the causative agents of the neglected tropical diseases human African trypanosomiasis (sleeping sickness) and Chagas disease, while exhibiting no cytotoxicity against human cell lines. Herein, we give a full account of our strategy evolution towards the synthesis of this structurally unique class of 12-membered macrolides, which culminated in the first total synthesis of (+)-actinoallolide A in 20 steps and 8% overall yield. Subsequent late-stage diversification then provided ready access to the congeneric (+)-actinoallolides B-E. Enabled by this flexible and efficient endgame sequence, we also describe the design and synthesis of a photoaffinity probe based on actinoallolide A to investigate its biological mode of action. This will allow ongoing labelling studies to identify their protein binding target(s). This journal is
Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies
Chen, Hao,Fu, Yuyin,Gou, Lantu,Guo, Cuiyu,Jiang, Xiaohua,Kang, Tairan,Lai, Qinhuai,Lai, Weirong,Liao, Wei,Lu, Ying,Peng, Yujia,Tao, Yiran,Wang, Ruixue,Wang, Xin,Wang, Yuxi,Wu, Mengdan,Yang, Jinliang,Yao, Yuqin,Yu, Lin,Zhang, Ruirui,Zhang, Yiwen,Zhang, Zhixiong
, (2020/05/11)
Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58–1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI–N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy.
