Late-stage chemoselective functional-group manipulation of bioactive natural products with super-electrophilic silylium ions

2017 ◽  
Vol 10 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Trandon A. Bender ◽  
Philippa R. Payne ◽  
Michel R. Gagné
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Bioactive Natural Products

scholarly journals Nickel-Catalyzed Three-Component Olefin Reductive Dicarbofunctionalization to Access Highly Functionalized Alkylborates

2020 ◽  
Author(s):  
Xiao-Xu Wang ◽  
Xi Lu ◽  
Shi-Jiang He ◽  
Yao Fu
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Coupling Efficiency ◽  
Convergent Synthesis ◽  
Drug Molecules ◽  
Aryl Iodides ◽  
Alkyl Bromides ◽  
Vinyl Boronates ◽  
Convenient Access

We report a three-component olefin reductive dicarbofunctionalization for constructing densely functionalized alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with versatile alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex, densely functionalized compounds.

Diversified synthesis and α-selective glycosylation of 3-amino-2,3,6-trideoxy sugars

2018 ◽  
Vol 5 (23) ◽  
pp. 3391-3395 ◽  
Author(s):  
Jing Zeng ◽  
Ruobin Wang ◽  
Wang Yao ◽  
Shuxin Zhang ◽  
Guangfei Sun ◽  
...  
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Bioactive Natural Products

Quick access to various unnatural 3-amino-2,3,6-trideoxy sugars was achieved by sequential functionalization of a glycal intermediate. This strategy and the further glycosylation method allowed the efficient late-stage modification of bioactive natural products and drugs.

scholarly journals Tyrosine and Drug-like Late-stage Benzylic Functionalization via Photoredox Catalysis

2020 ◽  
Author(s):  
Tobias Brandhofer ◽  
Volker Derdau ◽  
María Mendez ◽  
Christoph Pöverlein ◽  
Olga Garcia Mancheno
Keyword(s):  
Natural Products ◽  
Visible Light ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Functional Group ◽  
Reaction Conditions ◽  
Site Selectivity ◽  
Wide Range ◽  
High Yields ◽  
Therapeutic Compounds

Abstract Visible light mediated late-stage functionalization is a rising field in synthetic and medicinal chemistry, allowing the fast and diversified modification of valuable, potentially therapeutic compounds such as peptides. However, there are relatively few mild methodologies for the C(sp3)-H functionalization of complex peptides. Herein, we report a visible light mediated photocatalytic protocol for the benzylic C-H modification of tyrosine and related C-H bonds. The embraced radical-cation/deprotonation strategy enables an incorporation of a wide range of valuable functional groups in high yields and chemoselectivity. The mild reaction conditions, site-selectivity and high functional group tolerance was highlighted by the functionalization of complex peptides, drugs and natural products, providing a promising synthetic platform in medicinal chemistry.

scholarly journals Co-Catalyzed E-(β)-Selective Hydrogermylation of Terminal Alkynes

2021 ◽  
Author(s):  
Maxim Radzhabov ◽  
Neal Mankad
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Terminal Alkynes ◽  
Mechanistic Studies ◽  
Practical Utility ◽  
Π Complex ◽  
Accessible Method ◽  
High Yields

<a></a><a>We demonstrated unprecedentedly that Co complexes can catalyze hydrogermylation of alkynes. Subsequently, a selective, accessible method was developed to synthesize E-(β)-vinyl(trialkyl)germanes from various terminal alkynes with high yields. As shown on multiple examples, the developed method demonstrates broad functional group tolerance and practical utility for late-stage hydrogermylation of drugs and natural products. The method is compatible with alkynes bearing both aryl and alkyl substituents, providing unrivaled selectivity for previously challenging 1° alkyl-substituted alkynes. Moreover, the catalyst used in this method, Co<sub>2</sub>(CO)<sub>8</sub>, is a cheap and commercially available reagent. Conducted mechanistic studies supported syn-addition of Bu<sub>3</sub>GeH to an alkyne</a> π-complex.

scholarly journals Co-Catalyzed E-(β)-Selective Hydrogermylation of Terminal Alkynes

2021 ◽  
Author(s):  
Maxim Radzhabov ◽  
Neal Mankad
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Terminal Alkynes ◽  
Mechanistic Studies ◽  
Practical Utility ◽  
Π Complex ◽  
Accessible Method ◽  
High Yields

<a></a><a>We demonstrated unprecedentedly that Co complexes can catalyze hydrogermylation of alkynes. Subsequently, a selective, accessible method was developed to synthesize E-(β)-vinyl(trialkyl)germanes from various terminal alkynes with high yields. As shown on multiple examples, the developed method demonstrates broad functional group tolerance and practical utility for late-stage hydrogermylation of drugs and natural products. The method is compatible with alkynes bearing both aryl and alkyl substituents, providing unrivaled selectivity for previously challenging 1° alkyl-substituted alkynes. Moreover, the catalyst used in this method, Co<sub>2</sub>(CO)<sub>8</sub>, is a cheap and commercially available reagent. Conducted mechanistic studies supported syn-addition of Bu<sub>3</sub>GeH to an alkyne</a> π-complex.

scholarly journals The Enones as New Alkenyl Reagents via Ligand Promoted C–C Bonds Activation

2021 ◽  
Author(s):  
Hanyuan Li ◽  
Mei-Ling Wang ◽  
Yue-Wen Liu ◽  
Ling-Jun Li ◽  
Hui Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Bond Activation ◽  
Potential Utility ◽  
One Pot ◽  
Complex Molecules ◽  
The Past

Complementary to C–H bond activation, C–C bond activation has emerged over the past few years as an increasingly powerful tool to access and modify complex molecules. Ketones, owing to their versatility and availability, provide a significant platform for C–C bond activating reactions. Herein, we reported a <i>β</i>-carbon elimination strategy for alkene(sp<sup>2</sup>)–C(O) bonds to realize the olefination of unstrained enones via a vinyl palladium species, which delivers a series of conjugated polyene compounds. The protocol features broad substrate scope, excellent functional group tolerance and can be extended to dba (dibenzylideneacetone) substrates for olefination, alkynylation, arylation and amination, which demonstrates the generality of the approach and affords two valuable products in one pot. Furthermore, the late-stage functionalization of natural products (<i>β</i>-ionone and acetyl cedrene) and synthesis of natural products (piperine, lignarenone, novenone) highlight the potential utility of the reaction.

scholarly journals Nickel-Catalyzed Three-Component Olefin Reductive Dicarbofunctionalization to Access Highly Functionalized Alkylborates

2020 ◽  
Author(s):  
Xiao-Xu Wang ◽  
Xi Lu ◽  
Shi-Jiang He ◽  
Yao Fu
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Coupling Efficiency ◽  
Convergent Synthesis ◽  
Drug Molecules ◽  
Aryl Iodides ◽  
Alkyl Bromides ◽  
Vinyl Boronates ◽  
Convenient Access

We report a three-component olefin reductive dicarbofunctionalization for constructing densely functionalized alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with versatile alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex, densely functionalized compounds.

scholarly journals Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

2020 ◽  
Author(s):  
José Augusto Forni ◽  
NENAD MICIC ◽  
Timothy Connell ◽  
GEETHIKA WERAGODA ◽  
Anastasios Polyzos
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Aromatic Amines ◽  
Functional Group ◽  
Alkyl Halides ◽  
Catalytic Cycle ◽  
Aryl Bromides ◽  
Alkyl Iodides ◽  
Tertiary Alkyl

<p>We report a new visible light-mediated carbonylative amidation of aryl, heteroaryl and alkyl halides. A tandem catalytic cycle of [Ir(ppy)<sub>2</sub>(dtb-bpy)]<sup>+</sup> generates a potent iridium photoreductant via a second catalytic cycle in the presence of DIPEA which productively engages aryl bromides, iodides and even chlorides as well as primary, secondary and tertiary alkyl iodides. The versatility of the in-situ generated catalyst is illustrated by compatibility with aliphatic and aromatic amines, high functional group tolerance and the late-stage amidation of complex natural products. </p>

scholarly journals The Enones as New Alkenyl Reagents via Ligand Promoted C–C Bonds Activation

2021 ◽  
Author(s):  
Hanyuan Li ◽  
Mei-Ling Wang ◽  
Yue-Wen Liu ◽  
Ling-Jun Li ◽  
Hui Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Bond Activation ◽  
Potential Utility ◽  
One Pot ◽  
Complex Molecules ◽  
The Past

Complementary to C–H bond activation, C–C bond activation has emerged over the past few years as an increasingly powerful tool to access and modify complex molecules. Ketones, owing to their versatility and availability, provide a significant platform for C–C bond activating reactions. Herein, we reported a <i>β</i>-carbon elimination strategy for alkene(sp<sup>2</sup>)–C(O) bonds to realize the olefination of unstrained enones via a vinyl palladium species, which delivers a series of conjugated polyene compounds. The protocol features broad substrate scope, excellent functional group tolerance and can be extended to dba (dibenzylideneacetone) substrates for olefination, alkynylation, arylation and amination, which demonstrates the generality of the approach and affords two valuable products in one pot. Furthermore, the late-stage functionalization of natural products (<i>β</i>-ionone and acetyl cedrene) and synthesis of natural products (piperine, lignarenone, novenone) highlight the potential utility of the reaction.

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.

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