scholarly journals Two-Phase Total Synthesis of Taxanes: Tactics and Strategies

2020 ◽  
Vol 85 (16) ◽  
pp. 10293-10320
Author(s):  
Yuzuru Kanda ◽  
Yoshihiro Ishihara ◽  
Nathan C. Wilde ◽  
Phil S. Baran
Keyword(s):  
Total Synthesis ◽  
Two Phase

14-Step Synthesis of (+)-Ingenol from (+)-3-Carene

Science ◽  
2013 ◽  
Vol 341 (6148) ◽  
pp. 878-882 ◽  
Author(s):  
Lars Jørgensen ◽  
Steven J. McKerrall ◽  
Christian A. Kuttruff ◽  
Felix Ungeheuer ◽  
Jakob Felding ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Anticancer Activity ◽  
Actinic Keratosis ◽  
Skin Condition ◽  
Chemical Production ◽  
Two Phase ◽  
Chemical Complexity ◽  
Euphorbia Peplus ◽  
Stereocontrolled Synthesis ◽  
Phase Design

Ingenol is a diterpenoid with unique architecture and has derivatives possessing important anticancer activity, including the recently Food and Drug Administration–approved Picato, a first-in-class drug for the treatment of the precancerous skin condition actinic keratosis. Currently, that compound is sourced inefficiently from Euphorbia peplus. Here, we detail an efficient, highly stereocontrolled synthesis of (+)-ingenol proceeding in only 14 steps from inexpensive (+)-3-carene and using a two-phase design. This synthesis will allow for the creation of fully synthetic analogs of bioactive ingenanes to address pharmacological limitations and provides a strategic blueprint for chemical production. These results validate two-phase terpene total synthesis as not only an academic curiosity but also a viable alternative to isolation or bioengineering for the efficient preparation of polyoxygenated terpenoids at the limits of chemical complexity.

scholarly journals Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins Allowing a Formal Synthesis of Trichoderone A

2021 ◽  
Author(s):  
Oscar Gayraud ◽  
Benjamin Laroche ◽  
Nicolas Casaretto ◽  
Bastien Nay
Keyword(s):  
Total Synthesis ◽  
Claisen Rearrangement ◽  
Alder Reaction ◽  
Diels Alder ◽  
Two Phase ◽  
Formal Synthesis ◽  
Diels Alder Reaction ◽  
Oxidative Transformations ◽  
High Degree

Aspochalasins are leucine-derived cytochalasins. Their complexity is often associated to a high degree of biosynthetic oxidative transformations that could inspire a two-phase strategy in total synthesis. In that context, we describe the synthesis of a putative biomimetic tetracyclic intermediate. The key constructive steps are an intramolecular Diels-Alder reaction to install the characteristic isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement made on a highly unsaturated substrate. This work also constitutes a formal synthesis of trichoderone A.

scholarly journals Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins Allowing a Formal Synthesis of Trichoderone A

2021 ◽  
Author(s):  
Oscar Gayraud ◽  
Benjamin Laroche ◽  
Nicolas Casaretto ◽  
Bastien Nay
Keyword(s):  
Total Synthesis ◽  
Claisen Rearrangement ◽  
Alder Reaction ◽  
Diels Alder ◽  
Two Phase ◽  
Formal Synthesis ◽  
Diels Alder Reaction ◽  
Oxidative Transformations ◽  
High Degree

Aspochalasins are leucine-derived cytochalasins. Their complexity is often associated to a high degree of biosynthetic oxidative transformations that could inspire a two-phase strategy in total synthesis. In that context, we describe the synthesis of a putative biomimetic tetracyclic intermediate. The key constructive steps are an intramolecular Diels-Alder reaction to install the characteristic isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement made on a highly unsaturated substrate. This work also constitutes a formal synthesis of trichoderone A.

Two-Phase Synthesis of Taxol®

2020 ◽  
Author(s):  
Yuzuru Kanda ◽  
Hugh Nakamura ◽  
Shigenobu Umemiya ◽  
Ravi Kumar Puthukanoori ◽  
Venkata Ramana Murthy Appala ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Anticancer Agent ◽  
Synthetic Approach ◽  
Two Phase ◽  
Phase Synthesis ◽  
Natural Plant ◽  
Natural Isolates ◽  
Terpene Synthesis ◽  
The Subject ◽  
Biosynthetic Machinery

<p>Taxol® is widely regarded as amongst the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically-guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural- (plant</p> <p>material) or biosynthetically-derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol®.</p>

Two-Phase Synthesis of Taxol®

2020 ◽  
Author(s):  
Yuzuru Kanda ◽  
Hugh Nakamura ◽  
Shigenobu Umemiya ◽  
Ravi Kumar Puthukanoori ◽  
Venkata Ramana Murthy Appala ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Anticancer Agent ◽  
Synthetic Approach ◽  
Two Phase ◽  
Phase Synthesis ◽  
Natural Plant ◽  
Natural Isolates ◽  
Terpene Synthesis ◽  
The Subject ◽  
Biosynthetic Machinery

<p>Taxol® is widely regarded as amongst the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically-guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural- (plant</p> <p>material) or biosynthetically-derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol®.</p>

scholarly journals Two-Phase Terpene Total Synthesis: Historical Perspective and Application to the Taxol® Problem

Synlett ◽  
2010 ◽  
Vol 2010 (12) ◽  
pp. 1733-1745 ◽  
Author(s):  
Phil Baran ◽  
Yoshihiro Ishihara
Keyword(s):  
Total Synthesis ◽  
Historical Perspective ◽  
Two Phase

Effect of Shock Loading on the Microstructure of Uniloy 326

1974 ◽  
Vol 32 ◽  
pp. 504-505
Author(s):  
K. P. Staudhammer ◽  
L. E. Murr
Keyword(s):  
Grain Size ◽  
Shock Loading ◽  
Current Investigation ◽  
Two Phase ◽  
05 C ◽  
Shock Deformation ◽  
Heat Treated

The effect of shock loading on a variety of steels has been reviewed recently by Leslie. It is generally observed that significant changes in microstructure and microhardness are produced by explosive shock deformation. While the effect of shock loading on austenitic, ferritic, martensitic, and pearlitic structures has been investigated, there have been no systematic studies of the shock-loading of microduplex structures.In the current investigation, the shock-loading response of millrolled and heat-treated Uniloy 326 (thickness 60 mil) having a residual grain size of 1 to 2μ before shock loading was studied. Uniloy 326 is a two phase (microduplex) alloy consisting of 30% austenite (γ) in a ferrite (α) matrix; with the composition.3% Ti, 1% Mn, .6% Si,.05% C, 6% Ni, 26% Cr, balance Fe.

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