P(III) vs P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to an Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist

2021 ◽  
Author(s):  
Bin Zheng ◽  
Chao Hang ◽  
Jason Zhu ◽  
Geoffrey E. Purdum ◽  
Melda Sezen-Edmonds ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Cyclic Dinucleotide

scholarly journals P(III) vs. P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to An Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist

2021 ◽  
Author(s):  
Bin Zheng ◽  
Chao Hang ◽  
Jason Zhu ◽  
Geoffrey Purdum ◽  
Melda Sezen-Edmonds ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Functional Groups ◽  
Stereoselective Synthesis ◽  
Key Functional Groups ◽  
First Time ◽  
Cyclic Dinucleotide

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare, yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than sixteen-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

scholarly journals P(III) vs. P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to An Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist

2021 ◽  
Author(s):  
Bin Zheng ◽  
Chao Hang ◽  
Jason Zhu ◽  
Geoffrey Purdum ◽  
Melda Sezen-Edmonds ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Functional Groups ◽  
Stereoselective Synthesis ◽  
Key Functional Groups ◽  
First Time ◽  
Cyclic Dinucleotide

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare, yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than sixteen-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

2018 ◽  
Author(s):  
Marc Montesinos-Magraner ◽  
Matteo Costantini ◽  
Rodrigo Ramirez-Contreras ◽  
Michael E. Muratore ◽  
Magnus J. Johansson ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Chemical Space ◽  
Synthetic Approach ◽  
Asymmetric Cyclopropanation ◽  
Redox Active ◽  
Wide Range ◽  
Leaving Group ◽  
Stereoelectronic Properties ◽  
Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

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