scholarly journals Z-Selective Hydrofunctionalization of Dienes

2019 ◽  
Vol 2 (2) ◽  
pp. 77-78
Author(s):  
Clara Vicera ◽  
Raphael Dada ◽  
Rylan J. Lundgren
Keyword(s):  
Functional Groups ◽  
Internal Standard ◽  
Building Blocks ◽  
Biological Properties ◽  
Inert Atmosphere ◽  
Complex Molecules ◽  
Glucagon Receptor ◽  
Olefin Synthesis ◽  
Glucagon Receptor Antagonist ◽  
Treatment Of Diabetes

Olefins play a fundamental role in synthetic organic chemistry because they are useful building blocks that create molecules. However, geometry control (E- vs Z-) in olefin synthesis is of utmost importance because the olefin geometry has a tremendous impact on its physical, chemical and biological properties. Additionally, Z-olefins are less stable compared to their E-olefin counterparts; due to this difference, general methods to make olefins results in more cases of E-olefins production with relatively fewer Z-olefins caused by its instability. It has been reported that Z-olefins can be synthesized from dienes through a rhodium-catalyzed formate mediated transformation, with tolerance to several reducible functional groups.  With this successful method in hand, the focus is to make functionalized Z-alkenes while still maintaining tolerance to reducible functional groups under mild reaction conditions. Thus, this project presents the production of Z-olefins through rhodium-catalyzed hydrofunctionalization using the starting materials, dienes and aldehydes. This method requires an inert atmosphere and the reaction progress can be monitored by Nuclear Magnetic Resonance (NMR) using an internal standard to quantify the amount of product formed. In this process, it was observed that the starting material was consumed until more than 95% conversion. In addition, the possibility of using different dienes, such as diene esters and phenyl dienes, as well as different aldehydes could further broaden the scope of this method. The usefulness of this process can be applied to the production of complex molecules. For example, in the synthesis of a glucagon receptor antagonist, which is a drug that is used in the treatment of diabetes. Currently, there is a limited number of methods used to create Z-olefins; however, this proven procedure can be further applied in other hydrofunctionalization

scholarly journals Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery

2021 ◽  
Vol 14 (12) ◽  
pp. 1275
Author(s):  
Tony Ge ◽  
Jean-Christophe Cintrat
Keyword(s):  
Drug Discovery ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Building Blocks ◽  
Biological Properties ◽  
Extensive Review ◽  
Complex Molecules ◽  
New Chemical Entities ◽  
Amino Derivatives

Heterocyclic amino derivatives have been extensively synthesized and validated as potent bioactive compounds, and nowadays, numerous marketed drugs share these scaffolds, from very simple structures (monoamino, monocyclic compounds) to much more complex molecules (polycyclic derivatives with two or more nitrogen atoms within the (fused) rings). In a constant quest for new chemical entities in drug discovery, a few novel heterocycles have emerged in recent years as promising building blocks for the obtainment of bioactive modulators. In this context, pyrrolotriazinones have attracted attention, and some show promising biological activities. Here, we offer an extensive review of pyrrolo[2,1-f][1,2,4]triazin-4(1H)-one and pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one, describing their biological properties en route to drug discovery.

An Allosteric Glucagon Receptor Antagonist, LGD-6972, Displays Biased Receptor Signaling

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1117-P ◽  
Author(s):  
ERIC G. VAJDA ◽  
LIN ZHI ◽  
KEITH MARSCHKE
Keyword(s):  
Receptor Antagonist ◽  
Receptor Signaling ◽  
Glucagon Receptor ◽  
Glucagon Receptor Antagonist

Visible Light-Mediated Oxidative Debenzylation

2020 ◽  
Author(s):  
Cristian Cavedon ◽  
Eric T. Sletten ◽  
Amiera Madani ◽  
Olaf Niemeyer ◽  
Peter H. Seeberger ◽  
...  
Keyword(s):  
Reaction Time ◽  
Visible Light ◽  
Functional Groups ◽  
Continuous Flow ◽  
Protecting Groups ◽  
Benzyl Ether ◽  
Complex Molecules ◽  
Protective Groups ◽  
Benzyl Ethers ◽  
Harsh Conditions

Protecting groups are key in the synthesis of complex molecules such as carbohydrates to distinguish functional groups of similar reactivity. The harsh conditions required to cleave stable benzyl ether protective groups are not compatible with many other protective and functional groups. The mild, visible light-mediated debenzylation disclosed here renders benzyl ethers orthogonal protective groups. Key to success is the use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as stoichiometric or catalytic photooxidant such that benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes. The reaction time for this transformation can be reduced from hours to minutes in continuous flow. <br>

A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

2019 ◽  
Author(s):  
Patrick Fier ◽  
Kevin M. Maloney
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Building Blocks ◽  
Pharmaceutical Compounds ◽  
Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

2019 ◽  
Author(s):  
Patrick Fier ◽  
Kevin M. Maloney
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Building Blocks ◽  
Pharmaceutical Compounds ◽  
Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

scholarly journals Non-Enzymatic Desymmetrization Reactions in Aqueous Media

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 720
Author(s):  
Satomi Niwayama
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Functional Groups ◽  
Organic Compounds ◽  
Recent Progress ◽  
Aqueous Media ◽  
Building Blocks ◽  
Organic Reactions ◽  
Environmentally Benign ◽  
Enzymatic Desymmetrization

Symmetric organic compounds are generally obtained inexpensively, and therefore they can be attractive building blocks for the total synthesis of various pharmaceuticals and natural products. The drawback is that discriminating the identical functional groups in the symmetric compounds is difficult. Water is the most environmentally benign and inexpensive solvent. However, successful organic reactions in water are rather limited due to the hydrophobicity of organic compounds in general. Therefore, desymmetrization reactions in aqueous media are expected to offer versatile strategies for the synthesis of a variety of significant organic compounds. This review focuses on the recent progress of desymmetrization reactions of symmetric organic compounds in aqueous media without utilizing enzymes.

scholarly journals Thioesters Provide a Robust Path to Prebiotic Peptides

2021 ◽  
Author(s):  
Moran Frenkel-Pinter ◽  
Marcos Bouza ◽  
Facundo M. Fernández ◽  
Luke J. Leman ◽  
Loren Dean Williams ◽  
...  
Keyword(s):  
Building Blocks ◽  
Peptide Bond ◽  
Side Reactions ◽  
Peptide Bond Formation ◽  
One Pot ◽  
Complex Molecules ◽  
Peptide Formation ◽  
Wide Range ◽  
Amide Exchange ◽  
Prebiotic Earth

The condensation of building blocks into oligomers and polymers was an early and important stage in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic formation of peptides. Thioesters are hypothesized to have played key roles in prebiotic chemistry on early Earth, serving as energy storing molecules, as synthetic intermediates, and as catalysts in the formation of more complex molecules, including polypeptides. However, all abiotic reactions reported thus far for peptide formation via thioester intermediates have relied on activated building blocks or condensing agents, which are of questionable prebiotic relevance. We report robust, plausible prebiotic reactions of mercaptoacids with amino acids that result in the formation of peptides and thiodepsipeptides, which contain both peptide and thioester bonds. Peptide bond formation proceeds by the condensation of mercaptoacids to form thioesters followed by thioester-amide exchange. Mercaptoacids catalyze thiodepsipeptides and peptide formation under a wide range of pH conditions and at mild temperatures. Our results offer the most robust one-pot pathway for peptide formation ever reported. These results support the hypothesis that thiodepsipeptides formed robustly on prebiotic Earth and were possible contributors to early chemical evolution.

scholarly journals Mechanically axially chiral catenanes and noncanonical mechanically axially chiral rotaxanes

2022 ◽  
Author(s):  
Stephen Goldup ◽  
John Maynard ◽  
Peter Gallagher ◽  
David Lozano ◽  
Patrick Butler
Keyword(s):  
Building Blocks ◽  
Biological Properties ◽  
Mirror Image ◽  
Symmetry Properties ◽  
Covalently Bonded ◽  
Axially Chiral ◽  
Mechanical Bond ◽  
A Chain ◽  
Lord Kelvin ◽  
Molecular Rings

Abstract The term chiral was introduced by Lord Kelvin over a century ago to describe objects that are distinct from their own mirror image. Chirality is relevant in many scientific areas, but particularly chemistry because different mirror image forms of a molecule famously have different biological properties. Chirality typically arises in molecules due to a rigidly chiral arrangement of covalently bonded atoms. Less generally appreciated is that molecular chirality can arise when molecules are threaded through one another to create a mechanical bond. For example, when two molecular rings with chemically distinct faces are joined like links in a chain the resulting structure is chiral even when the rings themselves are not. We re-examined the symmetry properties of such mechanically axially chiral catenanes and in doing so identified a straightforward route to these molecules from simple building blocks. This also led to the discovery of a previously overlooked mechanical stereogenic unit that can arise when such a ring encircles a dumbbell-shaped axle to generate a rotaxane. These insights allowed us to produce the first highly enantioenriched axially chiral catenane and the same approach gave access to a molecule containing the newly identified noncanonical axially chiral rotaxane motif. With methods to access these structures in hand, the process of exploring their properties and applications can now begin.

scholarly journals Self assembled nanocages from DNA–protoporphyrin hybrid molecules

RSC Advances ◽  
2015 ◽  
Vol 5 (108) ◽  
pp. 89025-89029 ◽  
Author(s):  
Vandana Singh ◽  
Mohan Monisha ◽  
Roy Anindya ◽  
Prolay Das
Keyword(s):  
Functional Groups ◽  
Protoporphyrin Ix ◽  
Building Blocks ◽  
Carboxyl Groups ◽  
Dna Oligomers ◽  
Organic Hybrid ◽  
Molecular Building Blocks ◽  
Modified Dna ◽  
Hybrid Molecules ◽  
Self Assembled

DNA–organic hybrid molecular building blocks are generated by covalent conjugation of the carboxyl groups of protoporphyrin IX with the amine functional groups of modified DNA oligomers.

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