Traceless Solid-Phase Synthesis of Fused Chiral Macrocycles via Conformational Constraint-Assisted Cyclic Iminium Formation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73583791" target="_blank" >RIV/61989592:15110/17:73583791 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/17:73583791

Výsledek na webu

<a href="http://onlinelibrary.wiley.com/doi/10.1002/chem.201702461/epdf" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/chem.201702461/epdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.201702461" target="_blank" >10.1002/chem.201702461</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Traceless Solid-Phase Synthesis of Fused Chiral Macrocycles via Conformational Constraint-Assisted Cyclic Iminium Formation

Popis výsledku v původním jazyce

Natural products comprising chiral molecular scaffolds containing fused medium-sized cycles and macrocycles represent an important and relevant pharmacological target for the discovery and development of new drugs. Here, we describe traceless solid-phase synthesis of acyclic intermediates amenable to cyclization to medium (11) and large (12) fused rings. The key aspect of the synthetic strategy is incorporation of a specific conformation constraint that facilitates cyclization in favor of 11- and 12-membered rings rather than possible 7-membered ones. The role of constraints in preorganization required for cyclization is supported by computational analysis. The synthesis involves cyclic N-sulfonyliminium-nucleophilic addition chemistry as the key ring-forming reaction and proceeds with complete stereocontrol of the newly formed stereogenic center. We document the scope and limitations of this strategy in the synthesis of 11+5, 11+6, 11+7, and 12+6 fused rings representing molecular scaffolds with 3D architecture that mimic complex natural products.

Název v anglickém jazyce

Traceless Solid-Phase Synthesis of Fused Chiral Macrocycles via Conformational Constraint-Assisted Cyclic Iminium Formation

Popis výsledku anglicky

Natural products comprising chiral molecular scaffolds containing fused medium-sized cycles and macrocycles represent an important and relevant pharmacological target for the discovery and development of new drugs. Here, we describe traceless solid-phase synthesis of acyclic intermediates amenable to cyclization to medium (11) and large (12) fused rings. The key aspect of the synthetic strategy is incorporation of a specific conformation constraint that facilitates cyclization in favor of 11- and 12-membered rings rather than possible 7-membered ones. The role of constraints in preorganization required for cyclization is supported by computational analysis. The synthesis involves cyclic N-sulfonyliminium-nucleophilic addition chemistry as the key ring-forming reaction and proceeds with complete stereocontrol of the newly formed stereogenic center. We document the scope and limitations of this strategy in the synthesis of 11+5, 11+6, 11+7, and 12+6 fused rings representing molecular scaffolds with 3D architecture that mimic complex natural products.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry: A European Journal

ISSN

0947-6539

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

37

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

12876-12885

Kód UT WoS článku

000411033800028

EID výsledku v databázi Scopus

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