The Total Synthesis of Rhabdastrellic Acid A

2018 ◽  
Author(s):  
Yaroslav Boyko ◽  
Christopher Huck ◽  
David Sarlah
Keyword(s):  
Total Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Side Chains ◽  
General Strategy ◽  
Modular Approach ◽  
Linear Sequence ◽  
Generating Sequence ◽  
First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained <i>trans-syn-trans</i>-perhydrobenz[<i>e</i>]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a <i>p</i>-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

The Total Synthesis of Rhabdastrellic Acid A

2018 ◽  
Author(s):  
Yaroslav Boyko ◽  
Christopher Huck ◽  
David Sarlah
Keyword(s):  
Total Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Side Chains ◽  
General Strategy ◽  
Modular Approach ◽  
Linear Sequence ◽  
Generating Sequence ◽  
First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained <i>trans-syn-trans</i>-perhydrobenz[<i>e</i>]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a <i>p</i>-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
One Pot ◽  
Biologically Relevant ◽  
Cross Coupling Reactions ◽  
Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

scholarly journals A Revised Modular Approach to (-)-trans -Δ8 -THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Vol 2019 (12) ◽  
pp. 2289-2296 ◽  
Author(s):  
Victor R. L. J. Bloemendal ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
Thomas J. Boltje ◽  
Jan. C. M. van Hest ◽  
...  
Keyword(s):  
Late Stage ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
Cross Coupling Reactions

Towards the Total Synthesis of Schisandrene: Stereoselective Synthesis of the Dibenzocyclooctadiene Lignan Core

Synlett ◽  
2018 ◽  
Vol 29 (07) ◽  
pp. 908-911 ◽  
Author(s):  
K. Babu ◽  
Arramshetti Venkanna ◽  
Borra Poornima ◽  
Bandi Siva ◽  
B. Babu
Keyword(s):  
Total Synthesis ◽  
Stereoselective Synthesis ◽  
Asymmetric Reduction ◽  
Cross Coupling ◽  
Membered Ring ◽  
Stille Reaction ◽  
Reaction Sequence ◽  
Ring Closing Metathesis ◽  
Synthetic Strategy ◽  
First Time

A stereoselective synthesis of the dibenzocyclooctadiene ­lignan core of the natural product schisandrene is described. Starting from readily available gallic acid, the synthetic strategy involves Suzuki–Miyaura cross-coupling, Stille reaction, and ring-closing metathesis (RCM) in the reaction sequence. The required asymmetric center at C-7′ was established by an asymmetric reduction of a keto compound using the Corey–Bakshi–Shibata (CBS) catalyst. In our approach, the eight-membered ring was achieved by RCM for the first time.

First Total Synthesis of Pamamycin-621D

2018 ◽  
Vol 15 (1) ◽  
pp. 105-109 ◽  
Author(s):  
Hassan Norouzi-Arasi ◽  
Xavier J. Salom-Roig ◽  
Steve Lanners ◽  
Gilles Hanquet
Keyword(s):  
Total Synthesis ◽  
Optical Rotation ◽  
Large Family ◽  
Synthetic Approach ◽  
General Strategy ◽  
Structural Assignment ◽  
12 Steps ◽  
Aldol Addition ◽  
Additional Support ◽  
First Time

Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin- 621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Materials and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of 1H-NMR spectra with the natural pamamycin- 621D. Both optical rotation and 13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.

scholarly journals Boosting the in situ encapsulation of proteins with MIL-100(Fe): the role of strong Lewis acid centers

2021 ◽  
Author(s):  
Jesús Cases ◽  
Mónica Giménez-Marqués
Keyword(s):  
General Strategy ◽  
Triggered Release ◽  
Strong Lewis Acid ◽  
Metal Organic ◽  
Broad Variety ◽  
Acid Centers ◽  
First Time ◽  
Surface Nature

Encapsulation of biomolecules using Metal-Organic Frameworks (MOFs) to form stable biocomposites has been demonstrated a valuable strategy for their preservation and controlled release, which has been however restricted to specific electrostatic surface conditions. We present a general in situ strategy that promotes the spontaneous MOF growth onto a broad variety of proteins, for the first time, regardless of their surface nature. We demonstrate that MOFs based on cations exhibiting considerable inherent acidity such as MIL-100(Fe) enable biomolecule encapsulation, including alkaline proteins previously inaccesible by the welldeveloped in situ encapsulation with azolate-based MOFs. In particular, MIL-100(Fe) scaffold permits effective encapsulation of proteins with very distinct surface nature, retaining their activity and allowing triggered release under biocompatible conditions. This general strategy will enable an ample use of biomolecules in desired biolotechnological applications.

scholarly journals Intelligent wireless theranostic contact lens for close-loop electrical sensing and regulation of glaucoma

2021 ◽  
Author(s):  
Cheng Yang ◽  
Qianni Wu ◽  
Junqing Liu ◽  
Jingshan Mo ◽  
Xiangling Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Contact Lens ◽  
Closed Loop ◽  
Cross Coupling ◽  
Frequency Separation ◽  
Wireless Power ◽  
Electrical Sensing ◽  
Size Limits ◽  
First Time

Abstract Engineered closed-loop devices that can wirelessly track intraocular pressure (IOP) and offer feedback-medicine administrations are highly desirable for glaucoma treatments, yet remain difficult to develop. Integrated theranostic systems based on contact lens still confront several challenges, including size limits, requirements of wireless operations, and cross-coupling between multiple functional modulus. Here, for the first time to our knowledge, an integrated wireless theranostic contact lens (WTCL) for in situ electrical sensing and on-demand drug delivery of glaucoma was developed. The WTCL utilized a highly compact circuitry and structural design, which enabled high-degreed integration of IOP sensing and electrically controlled delivery modulus on the curved and limited surface of contact lens. The wireless IOP sensing modulus could ultra-sensitively detect IOP fluctuations, due to the unique cantilever configuration design of LCR circuit with ultra-soft air dielectric film sandwiched between each capacitive sensing plate. The drug delivery modulus employed a highly efficient wireless power transfer circuit, to trigger delivery of anti-glaucoma drug into aqueous chamber via iontophoresis to enhance drug permeation across cornea. The specialized design of frequency separation enabled individual operations of different modules without cross-coupling. The minimally invasive, smart, wireless and closed-loop theranostic features endowed the WTCL as a highly promising system for glaucoma treatments.

scholarly journals Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches

2021 ◽  
Author(s):  
Patrick Pfaff ◽  
Felix Anderl ◽  
Moritz Fink ◽  
Moritz Balkenhohl ◽  
Erick Carreira
Keyword(s):  
Natural Products ◽  
Arachidonic Acid ◽  
Modular Approach ◽  
Complex Molecules ◽  
Design And Synthesis ◽  
Wide Range ◽  
Potential Applications ◽  
First Time ◽  
Oriented Approach

We report a modular approach towards novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates. <i>In situ </i>desilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermal <i>Z</i>-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform that permits implementation of a consecutive and diversity-oriented approach linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and photoswitchable biotin conjugates

scholarly journals Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches

2021 ◽  
Author(s):  
Patrick Pfaff ◽  
Felix Anderl ◽  
Moritz Fink ◽  
Moritz Balkenhohl ◽  
Erick Carreira
Keyword(s):  
Natural Products ◽  
Arachidonic Acid ◽  
Modular Approach ◽  
Complex Molecules ◽  
Design And Synthesis ◽  
Wide Range ◽  
Potential Applications ◽  
First Time ◽  
Oriented Approach

We report a modular approach towards novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates. <i>In situ </i>desilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermal <i>Z</i>-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform that permits implementation of a consecutive and diversity-oriented approach linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and photoswitchable biotin conjugates

scholarly journals Concise Diastereoselective Total Synthesis of (±)-Parvistemonine A

Synlett ◽  
2020 ◽  
Vol 31 (18) ◽  
pp. 1800-1804
Author(s):  
Kazuyuki Sugita ◽  
Rintaro Matsuo ◽  
Ayumu Miyashita ◽  
Motoi Kuwabara ◽  
Shinya Adachi ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Michael Addition ◽  
Wittig Reaction ◽  
Crystallographic Analysis ◽  
Mitsunobu Reaction ◽  
X Ray ◽  
Linear Sequence ◽  
Relative Stereochemistry ◽  
Key Steps ◽  
First Time

AbstractWe have developed a concise diastereoselective total synthesis of (±)-parvistemonine A. By using a Mukaiyama–Michael addition, an aza-Wittig reaction, a Paal–Knorr pyrrole synthesis, an acid-mediated annulation, and a Mitsunobu reaction as key steps, we achieved a total synthesis in which the longest linear sequence was ten steps and the overall yield was 19.6%. Additionally, the relative stereochemistry of parvistemonine A was confirmed by X-ray crystallographic analysis for the first time.

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