Recent Advances in the Total Synthesis of Polyketide Natural Products as Promising Anticancer Agents

2009 ◽  
Vol 62 (7) ◽  
pp. 624 ◽  
Author(s):  
Ian Paterson ◽  
Alison D. Findlay
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
Therapeutic Agents ◽  
Natural Abundance ◽  
Spongistatin 1 ◽  
Lead Compounds ◽  
Altohyrtin A ◽  
Synthetic Routes

A growing number of complex polyketides, isolated from a variety of marine and terrestrial sources, present novel scaffolds for the development of cancer therapeutic agents. However, the low natural abundance of such lead compounds often precludes full biological evaluation, which demands the development of efficient synthetic routes to afford a sustainable supply. In this account, we provide an overview of the total synthesis of several representative anticancer polyketides – dolastatin 19, spirangien A, reidispongiolide A, and spongistatin 1/altohyrtin A – based on versatile aldol methodology developed in our group.

The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: fragment couplings, completion of the synthesis, analogue generation and biological evaluation

2005 ◽  
Vol 3 (13) ◽  
pp. 2431 ◽  
Author(s):  
Ian Paterson ◽  
David Y.-K. Chen ◽  
Mark J. Coster ◽  
José L. Aceña ◽  
Jordi Bach ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Biological Evaluation ◽  
Spongistatin 1 ◽  
Altohyrtin A

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

scholarly journals Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents

2020 ◽  
Vol 56 (10) ◽  
pp. 1529-1532
Author(s):  
Talia R. Pettigrew ◽  
Rachel J. Porter ◽  
Stephen J. Walsh ◽  
Michael P. Housden ◽  
Nelson Y. S. Lam ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
Sar Studies ◽  
Synthesis And Biological Evaluation

Analysis of bound structures and SAR studies led to the function-oriented simplification of the aplyronines; a convergent and modular synthetic platform then enabled the total synthesis and biological evaluation of four novel analogues.

Total synthesis and biological evaluation of ustiloxin natural products and two analogs

2006 ◽  
Vol 16 (18) ◽  
pp. 4804-4807 ◽  
Author(s):  
Pixu Li ◽  
Cory D. Evans ◽  
Erin M. Forbeck ◽  
Haengsoon Park ◽  
Ruoli Bai ◽  
...  
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation

Stereocontrolled Total Synthesis of (+)-Altohyrtin A/Spongistatin 1

2001 ◽  
Vol 113 (21) ◽  
pp. 4179-4184 ◽  
Author(s):  
Ian Paterson ◽  
David Y.-K. Chen ◽  
Mark J. Coster ◽  
Jose L. Aceña ◽  
Jordi Bach ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Spongistatin 1 ◽  
Altohyrtin A

Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds

2018 ◽  
Vol 16 (35) ◽  
pp. 6372-6390 ◽  
Author(s):  
Saumitra Sengupta ◽  
Goverdhan Mehta
Keyword(s):  
Natural Products ◽  
Cyclic Amp ◽  
Total Synthesis ◽  
Natural Product ◽  
Lead Compounds ◽  
Camp Pathway

Natural product modulators of the cAMP pathway have been evaluated and their total synthesis campaign is described in detail.

scholarly journals Profiled tea extracts exemplifying the importance of characterizing food bioactives: opinion piece

2019 ◽  
Vol 5 ◽  
pp. 1-5 ◽  
Author(s):  
Shiming Li ◽  
Alexander Gosslau ◽  
Klaus Lange ◽  
Chi-Tang Ho
Keyword(s):  
Natural Products ◽  
Single Molecule ◽  
Functional Foods ◽  
Biological Effects ◽  
Biological Evaluation ◽  
Therapeutic Agents ◽  
Therapeutic Effects ◽  
Chemical Identification ◽  
Component Identification

Natural products from food and herbs have been used as functional food and medicine for centuries, much earlier than any of the current single molecule drugs in the market. Historically, natural products are the dominant resources of current global pharmaceutical market. Examples include world’s most commonly used drugs such as aspirin, penicillin and taxol. In viewing the increasing attraction and exponentially growing need for functional foods and effective medicines, the potential for natural products to serve as safe and effective preventive and therapeutic agents is of much interest. However, the importance in the phytochemical characterization of plant origin and associated extracts containing multiple phytochemicals in research and product development in this field has been plagued by overwhelmingly focusing on their biological effects. More than often inconsistent and invalid biological results are provided without chemical component identification and validation. Hence it is vital to characterize and identify the ingredients in the plant extracts – food bioactives- that play critical roles in promoting health or having therapeutic effects. The combination of chemical identification and biological evaluation is the key to having valid and consistent results in elucidating health beneficial properties of a plant or its extracts and also a key to have a meaningful comparison among similar studies due to the use of the same standard. Herein, we use tea as examples demonstrating the importance of phytochemical profiling and associated bioactive property of functional foods.

Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog

2019 ◽  
Vol 24 (36) ◽  
pp. 4251-4269 ◽  
Author(s):  
Rocco Palermo ◽  
Francesca Ghirga ◽  
Maria Grazia Piccioni ◽  
Flavia Bernardi ◽  
Nadezda Zhdanovskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Chemical Biology ◽  
Total Syntheses ◽  
Lead Compounds ◽  
Promising Strategy ◽  
Anticancer Drug Discovery

It is nowadays widely accepted that some tumors have a niche of cells endowed with stemness features, which may cause resistance to conventional anticancer therapies and relapse/recurrence of the malignancy. These cells are usually referred to as cancer stem cells (CSCs) and, different from normal cancer cells, are rather quiescent. Targeting CSCs is thus a highly challenging but promising strategy to counteract tumor growth, and to develop innovative anticancer agents. Here, we review the chemical, biological and multidisciplinary efforts that have been spent in targeting CSCsspecific signaling pathways Notch and Hedgehog (Hh) for anticancer drug discovery. In particular, the use of natural products as a valuable source of lead compounds or chemical biology tools is emphasized. Examples of natural products functionalization through semi-synthetic transformations or total syntheses, aimed at improving pharmacokinetics and/or pharmacodynamics properties of natural products in Notch or Hh inhibition, are provided as well.

scholarly journals Total Synthesis and Biological Evaluation of Phaeosphaerides

Catalysts ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 206 ◽  
Author(s):  
Kenichi Kobayashi ◽  
Kosaku Tanaka ◽  
Hiroshi Kogen
Keyword(s):  
Crystal Structure ◽  
Natural Products ◽  
Total Synthesis ◽  
Structure Analysis ◽  
Endophytic Fungus ◽  
Biological Evaluation ◽  
Crystal Structure Analysis ◽  
X Ray ◽  
Structure Activity ◽  
Synthesis And Biological Evaluation

This article reviews studies regarding the total synthesis of phaeosphaerides A and B, nitrogen-containing bicyclic natural products isolated from an endophytic fungus. Numerous synthetic efforts and an X-ray crystal structure analysis of phaeosphaeride A have enabled revision of its originally proposed structure. In addition, a successful protic acid-mediated transformation of phaeosphaeride A to phaeosphaeride B revealed the hypothetical biosynthesis of phaeosphaeride B from phaeosphaeride A. Structure–activity relationship studies of phaeosphaeride derivatives are also discussed.

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