scholarly journals Towards the Synthesis of Hybrid Peloruside A and Laulimalide Analogues

2021 ◽  
Author(s):  
◽  
Febly Tho
Keyword(s):  
Natural Product ◽  
Anticancer Agent ◽  
Structural Complexity ◽  
Coupling Reaction ◽  
Marine Natural Product ◽  
Peloruside A ◽  
Biological Analysis ◽  
M Phase ◽  
Similar Mode ◽  
Mycale Hentscheli

<p>(+)-Peloruside A is a novel cytotoxic marine natural product isolated from the New Zealand sponge Mycale hentscheli(42). Peloruside A is a potential anticancer agent that has a similar mode of action to that of the successful drug paclitaxel. Biological analysis indicated that (+)-peloruside A promotes tubulin hyperassembly and cellular microtubule stabilisation which lead to mitosis blockage in the G2/M phase of the cell cycle and consequent cell apoptosis(43),(47). (-)-Laulimalide is also a cytotoxic natural product with microtubule stabilising bioactivity, and is a potential anticancer agent(47). Biological analysis showed that (+)-peloruside A and (-)-laulimalide are competitive, suggesting that they bind to the same active site(47). (+)-Peloruside A and (-)-laulimalide also display synergy with taxoids(47). Due to the structural complexity of peloruside A, our research has focused on developing an analogue 151 for ease of synthesis. Thus, the simplified C5-C9 dihydropyran moiety of (-)-laulimalide, with fewer stereocentres than that of (+)-peloruside A, has been incorporated into analogue 151 whilst retaining the 16- membered ring backbone of (+)-peloruside A. The proposed synthesis of 151 involves a Yamaguchi macrolactonization, a 1,5-anti-aldol coupling, and a ring closing metathesis as key reactions. This thesis reports on the synthesis of key fragments of analogue 151 and the crucial 1,5-anti-aldol coupling reaction for the assembly of the carbon backbone.</p>

scholarly journals Towards the Synthesis of Hybrid Peloruside A and Laulimalide Analogues

2021 ◽  
Author(s):  
◽  
Febly Tho
Keyword(s):  
Natural Product ◽  
Anticancer Agent ◽  
Structural Complexity ◽  
Coupling Reaction ◽  
Marine Natural Product ◽  
Peloruside A ◽  
Biological Analysis ◽  
M Phase ◽  
Similar Mode ◽  
Mycale Hentscheli

<p>(+)-Peloruside A is a novel cytotoxic marine natural product isolated from the New Zealand sponge Mycale hentscheli(42). Peloruside A is a potential anticancer agent that has a similar mode of action to that of the successful drug paclitaxel. Biological analysis indicated that (+)-peloruside A promotes tubulin hyperassembly and cellular microtubule stabilisation which lead to mitosis blockage in the G2/M phase of the cell cycle and consequent cell apoptosis(43),(47). (-)-Laulimalide is also a cytotoxic natural product with microtubule stabilising bioactivity, and is a potential anticancer agent(47). Biological analysis showed that (+)-peloruside A and (-)-laulimalide are competitive, suggesting that they bind to the same active site(47). (+)-Peloruside A and (-)-laulimalide also display synergy with taxoids(47). Due to the structural complexity of peloruside A, our research has focused on developing an analogue 151 for ease of synthesis. Thus, the simplified C5-C9 dihydropyran moiety of (-)-laulimalide, with fewer stereocentres than that of (+)-peloruside A, has been incorporated into analogue 151 whilst retaining the 16- membered ring backbone of (+)-peloruside A. The proposed synthesis of 151 involves a Yamaguchi macrolactonization, a 1,5-anti-aldol coupling, and a ring closing metathesis as key reactions. This thesis reports on the synthesis of key fragments of analogue 151 and the crucial 1,5-anti-aldol coupling reaction for the assembly of the carbon backbone.</p>

scholarly journals Developing a scalable synthesis of Peloruside A

2021 ◽  
Author(s):  
◽  
Amira Brackovic
Keyword(s):  
Large Scale ◽  
Multidrug Resistant ◽  
Marine Natural Product ◽  
Protecting Group ◽  
Peloruside A ◽  
Synthetic Strategy ◽  
Cancerous Cell ◽  
Scalable Synthesis ◽  
Future Work ◽  
Mycale Hentscheli

<p>Peloruside A (PelA, 1) is a marine natural product isolated from a sponge Mycale hentscheli found in Pelorus Sound, New Zealand. It is a microtubule-stabilising agent, active against various cancerous cell lines at nanomolar concentrations and offers several advantages over the current drugs on the market due to its unique mode of microtubule stabilisation, its potency and its activity in multidrug resistant cells. Since large-scale isolation of the compound from the sponge is unsustainable and an attempt to grow the sponge failed due to a sea-slug infestation, devising an efficient synthesis of peloruside A that will be able to deliver larger quantities of this compound is essential in order to conduct further studies and enable the eventual manufacture of the drug.   Peloruside A is also a very interesting synthetic target as a macrolide with ten stereogenic centres, an internal pyran ring and a trisubstituted Z-double bond. Our synthetic strategy combines elements from previous total and partial syntheses with novel elements with an aim to make the synthesis more efficient. The synthesis of the side-chain fragment (C12–C20) was based on Evans' methodology1 which was also utilised to couple this fragment with the C8–C11 fragments. It was envisioned to evaluate two different end-game strategies, and to this end it was necessary to synthesise two different versions of the C8–C11 fragment. However, the synthesis of the C1–C7 fragments proved to be quite challenging and required a lot of alterations to the synthetic plan and the protecting group strategy. Various routes based on previous syntheses by Ghosh, Jacobsen and Taylor were explored.2–4 Eventually, the key intermediate was synthesised using a modified Taylor methodology. Our future work will focus on optimising and establishing fragment coupling methodologies and evaluating the two end-game approaches: macrolactonisation and a ring-closing metathesis.</p>

scholarly journals Developing a scalable synthesis of Peloruside A

2021 ◽  
Author(s):  
◽  
Amira Brackovic
Keyword(s):  
Large Scale ◽  
Multidrug Resistant ◽  
Marine Natural Product ◽  
Protecting Group ◽  
Peloruside A ◽  
Synthetic Strategy ◽  
Cancerous Cell ◽  
Scalable Synthesis ◽  
Future Work ◽  
Mycale Hentscheli

<p>Peloruside A (PelA, 1) is a marine natural product isolated from a sponge Mycale hentscheli found in Pelorus Sound, New Zealand. It is a microtubule-stabilising agent, active against various cancerous cell lines at nanomolar concentrations and offers several advantages over the current drugs on the market due to its unique mode of microtubule stabilisation, its potency and its activity in multidrug resistant cells. Since large-scale isolation of the compound from the sponge is unsustainable and an attempt to grow the sponge failed due to a sea-slug infestation, devising an efficient synthesis of peloruside A that will be able to deliver larger quantities of this compound is essential in order to conduct further studies and enable the eventual manufacture of the drug.   Peloruside A is also a very interesting synthetic target as a macrolide with ten stereogenic centres, an internal pyran ring and a trisubstituted Z-double bond. Our synthetic strategy combines elements from previous total and partial syntheses with novel elements with an aim to make the synthesis more efficient. The synthesis of the side-chain fragment (C12–C20) was based on Evans' methodology1 which was also utilised to couple this fragment with the C8–C11 fragments. It was envisioned to evaluate two different end-game strategies, and to this end it was necessary to synthesise two different versions of the C8–C11 fragment. However, the synthesis of the C1–C7 fragments proved to be quite challenging and required a lot of alterations to the synthetic plan and the protecting group strategy. Various routes based on previous syntheses by Ghosh, Jacobsen and Taylor were explored.2–4 Eventually, the key intermediate was synthesised using a modified Taylor methodology. Our future work will focus on optimising and establishing fragment coupling methodologies and evaluating the two end-game approaches: macrolactonisation and a ring-closing metathesis.</p>

Progress Toward The Total Synthesis Of The Marine Natural Product Karlotoxin 5

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
M Albadry ◽  
Y Zou ◽  
Y Takahashi ◽  
A Waters ◽  
M Hossein ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Marine Natural Product

Actin-binding Comparisons of the Marine Natural Product Latrunculin B with Natural and Semi-synthetic Latrunculin B Analogs

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
JJ Bowling ◽  
PR Daga ◽  
S Odde ◽  
SA Ahmed ◽  
MK Mesbah ◽  
...  
Keyword(s):  
Natural Product ◽  
Marine Natural Product ◽  
Actin Binding ◽  
Latrunculin B

Synthesis and antibacterial activities of marine natural product Ianthelliformisamines and subereamine synthetic analogues

2021 ◽  
pp. 127883
Author(s):  
Shivaji Narayan Khadake ◽  
Shaik Karamathulla ◽  
Tapan Kumar Jena ◽  
Mohan Monisha ◽  
Nikhil Kumar Tuti ◽  
...  
Keyword(s):  
Natural Product ◽  
Antibacterial Activities ◽  
Marine Natural Product ◽  
Synthetic Analogues

Chirality Transfer from a Chiral Primary Alcohol Equivalent Through Allyl Cyanate-to-Isocyanate Rearrangement: Synthesis of (+)-Geranyllinaloisocyanide

Synthesis ◽  
2019 ◽  
Vol 51 (15) ◽  
pp. 2959-2964 ◽  
Author(s):  
Yoshiyasu Ichikawa ◽  
Hirofumi Morimoto ◽  
Toshiya Masuda
Keyword(s):  
Natural Product ◽  
Primary Alcohol ◽  
Marine Natural Product ◽  
Chirality Transfer ◽  
New Approach ◽  
Stereogenic Centers ◽  
Quaternary Stereogenic Centers

A new approach was developed to construct quaternary stereogenic centers bearing nitrogen substituents in an enantioselective manner. The strategy takes advantage of [1,3]-chirality transfer from a chiral primary alcohol equivalent through an allyl cyanate-to-isocyanate rearrangement. This approach was employed in an efficient eight-step synthesis of the marine natural product, (+)-geranyllinaloisocyanide, in 43% overall yield.

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