scholarly journals Site-switchable mono-O-allylation of polyols

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hua Tang ◽  
Yu-Biao Tian ◽  
Hongyan Cui ◽  
Ren-Zhe Li ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Groups ◽  
Lewis Acid ◽  
Grand Challenge ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Bioactive Natural Products ◽  
Direct Derivatization ◽  
A Site ◽  
Site Selective

Abstract Site-selective modification of complex molecules allows for rapid accesses to their analogues and derivatives, and, therefore, offers highly valuable opportunities to probe their functions. However, to selectively manipulate one out of many repeatedly occurring functional groups within a substrate represents a grand challenge in chemistry. Yet more demanding is to develop methods in which alterations to the reaction conditions lead to switching of the specific site of reaction. We report herein the development of a Pd/Lewis acid co-catalytic system that achieves not only site-selective, but site-switchable mono-O-allylation of polyols with readily available reagents and catalysts. Through exchanging the Lewis acid additives that recognize specific hydroxyls in a polyol substrate, our system managed to install a versatile allyl group to the target in a site-switchable manner. Our design demonstrates remarkable scope, and is amenable to the direct derivatization of various complex, bioactive natural products.

scholarly journals Site-Selective C-C Modification of Proteins at Neutral pH Using Organocatalyst-Mediated Cross Aldol Ligations

2018 ◽  
Author(s):  
Martin A. Fascione ◽  
Richard J. Spears ◽  
Robin L. Brabham ◽  
Darshita Budhadev ◽  
Tessa Keenan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Stable Carbon ◽  
Biological Mechanisms ◽  
Large Excess ◽  
Reaction Conditions ◽  
Chemical Methods ◽  
Neutral Ph ◽  
Chemical Modification Of Proteins ◽  
A Site ◽  
Site Selective

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing dynamic biological mechanisms. The general use of chemical methods for the functionalisation of proteins remains limited however by the frequent requirement for complicated reaction partners to be present in large excess, and harsh reaction conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH under biocompatible conditions. OPAL enables rapid chemical modification of proteins within an hour using simple aldehyde probes in minimal excess, and is utilised here in the selective affinity tagging of proteins in cell lysate. Furthermore we demonstrate that the b-hydroxy aldehyde product of the OPAL can be functionalised a second time at neutral pH in a subsequent organocatalyst-mediated oxime ligation. This tandem strategy is showcased in the ‘chemical mimicry’ of a previously inaccessible natural dual post-translationally modified protein integral to the pathogenesis of the neglected tropical disease Leishmaniasis. <br>

Oxidative cyclization for the synthesis of complex tetrahydrofuran-containing natural products

2013 ◽  
Vol 85 (6) ◽  
pp. 1175-1184 ◽  
Author(s):  
Robert D. C. Pullin ◽  
Radosław M. Lipiński ◽  
Timothy J. Donohoe
Keyword(s):  
Natural Products ◽  
Amino Acid ◽  
Functional Groups ◽  
Lewis Acid ◽  
Excitatory Amino Acid ◽  
Oxidative Cyclization ◽  
Annonaceous Acetogenins ◽  
Hydride Shift ◽  
Vicinal Diols ◽  
Shift Sequence

The osmium-catalyzed oxidative cyclization of vicinal diols onto proximal olefins to generate 2,5-cis-substituted tetrahydrofurans (THFs) has been exploited as the key step for the construction of several complex THF-containing natural products, namely, the annonaceous acetogenins cis-sylvaticin, sylvaticin, and the excitatory amino acid neo-dysiherbaine A. Recently modified conditions that employ a Lewis acid enable the cyclization to proceed under milder conditions, providing greater tolerance to acid-sensitive functional groups, as demonstrated in two of the syntheses. Flexibility for the construction of 2,5-trans-THFs was demonstrated in the synthesis of sylvaticin by utilization of an intramolecular hydride-shift sequence.

scholarly journals Site-Selective C-C Modification of Proteins at Neutral pH Using Organocatalyst-Mediated Cross Aldol Ligations

2018 ◽  
Author(s):  
Martin A. Fascione ◽  
Richard J. Spears ◽  
Robin L. Brabham ◽  
Darshita Budhadev ◽  
Tessa Keenan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Stable Carbon ◽  
Biological Mechanisms ◽  
Large Excess ◽  
Reaction Conditions ◽  
Chemical Methods ◽  
Neutral Ph ◽  
Chemical Modification Of Proteins ◽  
A Site ◽  
Site Selective

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing dynamic biological mechanisms. The general use of chemical methods for the functionalisation of proteins remains limited however by the frequent requirement for complicated reaction partners to be present in large excess, and harsh reaction conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH under biocompatible conditions. OPAL enables rapid chemical modification of proteins within an hour using simple aldehyde probes in minimal excess, and is utilised here in the selective affinity tagging of proteins in cell lysate. Furthermore we demonstrate that the b-hydroxy aldehyde product of the OPAL can be functionalised a second time at neutral pH in a subsequent organocatalyst-mediated oxime ligation. This tandem strategy is showcased in the ‘chemical mimicry’ of a previously inaccessible natural dual post-translationally modified protein integral to the pathogenesis of the neglected tropical disease Leishmaniasis. <br>

scholarly journals Chemo- and site-selective derivatizations of natural products enabling biological studies

2014 ◽  
Vol 31 (3) ◽  
pp. 318-334 ◽  
Author(s):  
Omar Robles ◽  
Daniel Romo
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Reactive Group ◽  
Bioactive Natural Products ◽  
Sar Studies ◽  
Structure Activity ◽  
Biological Studies ◽  
Site Selective

The direct chemo- and site-selective modification of native bioactive natural products (NP) for structure–activity relationship (SAR) studies and cellular probe synthesis has recently begun to be addressed (FG = functional group). This review highlights selected recent examples of these functionalization strategies, including those that simultaneously introduce a linker and reactive group (gray structure) for subsequent conjugation to reporter tags.

scholarly journals The Combination of Lewis Acid with N-Heterocyclic Carbene (NHC) Catalysis

Catalysts ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 863 ◽  
Author(s):  
Qianfa Jia ◽  
Yaqiong Li ◽  
Yinhe Lin ◽  
Qiao Ren
Keyword(s):  
Natural Products ◽  
Asymmetric Synthesis ◽  
Lewis Acid ◽  
Reaction Conditions ◽  
Recent Advances ◽  
Enantioselective Reactions ◽  
Ready Availability ◽  
Chiral Pharmaceuticals ◽  
Powerful Strategy ◽  
Operational Simplicity

In the last ten years, the combination of Lewis acid with N-heterocyclic carbene (NHC) catalysis has emerged as a powerful strategy in a variety of important asymmetric synthesis, due to the ready availability of starting materials, operational simplicity and mild reaction conditions. Recent findings illustrate that Lewis acid could largely enhance the efficiency and enantioselectivity, reverse the diastereoselectivity, and even influence the pathway of the same reaction partners. Herein, this review aims to reveal the recent advances in NHC-Lewis acid synergistically promoted enantioselective reactions for the expeditious assembly of versatile biologically important chiral pharmaceuticals and natural products.

New Strategies for Activation of Phosphonates/Phosphates to Forge Functional Phosphorus Compounds

Synlett ◽  
2019 ◽  
Vol 30 (06) ◽  
pp. 635-641 ◽  
Author(s):  
Jun Kang ◽  
Hai Huang
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Natural Compounds ◽  
Synthetic Methods ◽  
Phosphorus Compounds ◽  
Reaction Conditions ◽  
Structural Motifs ◽  
Bioactive Natural Products ◽  
Potential Applications ◽  
New Strategies

Organophosphonate analogues are important structural motifs that are present in bioactive natural products, pharmaceuticals, and agrochemicals. Because they are useful in a broad range of applications, much effort has focused on developing efficient synthetic methods that enable access to organophosphonates and their derivatives. However, currently available synthetic procedures rely on harsh reaction conditions and are limited to a narrow substrate scope. Our lab has recently made important advances in leveraging inert phosphonates/phosphates into functional phosphorus compounds such as mixed phosphonates, phosphates, and mixed aryl phosphate derivatives. Presented herein is an overview of recent achievements in the synthesis of phosphonate/phosphate derivatives and a summary of our recent accomplishments in Tf2O-promoted activating strategy of phosphonate analogues.1 Introduction2 Direct Activating Strategy of Phosphonate Analogues3 Late-stage Phosphonylation of Natural Compounds4 Potential Applications5 Summary

scholarly journals Zinc (II)-Mediated Selective O-Benzylation of 2-Oxo-1,2-Dihydropyridines Systems

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1784 ◽  
Author(s):  
Qifan Zhou ◽  
Fangyu Du ◽  
Xinjie Liang ◽  
Wenqiang Liu ◽  
Ting Fang ◽  
...  
Keyword(s):  
Natural Products ◽  
Ternary System ◽  
Functional Groups ◽  
Organic Synthesis ◽  
Critical Role ◽  
New Method ◽  
Reaction Conditions ◽  
Highly Effective ◽  
Benzyl Halides ◽  
Synthetic Intermediates

The selective O-benzylation of 2-oxo-1,2-dihydropyridines plays a critical role in organic synthesis of natural products and biological active molecules. Herein we report a novel ternary system of ZnO, ZnCl2 and N,N-diisopropylethylamine (DIEA), that is highly effective for selective O-benzylation of 2-oxo-1,2-dihydropyridines using abundant substituted benzyl halides and related substituted 2-oxo-1,2-dihydropyridines compounds. This process allows access to a variety of O-benzyl products under mild reaction conditions, which are important synthetic intermediates in the protection of functional groups, and represents a new method toward the development for the O-benzylation of 2-oxo-1,2-dihydropyridines.

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