TY - JOUR

T1 - Highly Selective Gold-Catalyzed Cycloisomerization of Furanolabdanoid Dialkynes with Alkynyl Substituents in the Furan Ring

AU - Kharitonov, Yurii

AU - Shakirov, Makhmut M.

AU - Shults, Elvira E.

PY - 2018

Y1 - 2018

N2 - Aim and Objective: We studied the synthesis of new groups of functionalized isobenzofurans and isoindolines by selective gold catalyzed cycloisomerization of some new optically active furandialkynes derived from the natural furanolabdanoid lambertianic acid. Functionalized isobenzofurans and isoindolines are considered as privileged structures that are currently experiencing a renewed interest in medicinal chemistry.Materials and Methods: Using the AuCl3-catalyzed cycloisomerization of furanolabdanoid dialkynes we synthesized several new groups of biologically interested isobenzofurans and isoindolines with labdanoid substitution. The structure of all new compounds was proven by elemental and spectral analysis: IR, mass-, and NMR data.Results: The synthesis of 15,16-dialkynyl substituted furanolabdanoids was carried out. Au(III)-Catalyzed cycloisomerization of those compounds proceeded highly selectively with the formation of optically active 4-substituted 7-hydroxy-3(6)-propargylaminomethylisobenzofurans or 7-hydroxy-3(6)-propargyloxymethylisoindolines. The cycloisomerization of the 15-(prop-2-yn-l-yloxymethyl)-16-((N-p-toluenesulfonyl)-prop2-yn-1-ylaminomethyl)labdatriene proceeded in part on the 15 position and involved the previously unknown intramolecular transfer of N-(p-toluenesulfonyl)propargylaminomethyl substituent to the oxygen in the stage of formation of an aromatic ring. A feasible reaction mechanism for this transformation is presented. It was revealed that the conversion of labdanoid furan-15-ynes to 1,3-dihydroisobenzofurans depends on the nature of the substituent in the 16 position of the furanolabdanoid.Conclusions: The present study sheds light on the Au(III)-catalyzed cycloisomerization of new group of highly functionalized furandialkynes. Also, new groups of alkynyloxymethyl or alkynylaminomethyl substituted optically active isobenzofurans and isoindolines were obtained and fully characterized.

AB - Aim and Objective: We studied the synthesis of new groups of functionalized isobenzofurans and isoindolines by selective gold catalyzed cycloisomerization of some new optically active furandialkynes derived from the natural furanolabdanoid lambertianic acid. Functionalized isobenzofurans and isoindolines are considered as privileged structures that are currently experiencing a renewed interest in medicinal chemistry.Materials and Methods: Using the AuCl3-catalyzed cycloisomerization of furanolabdanoid dialkynes we synthesized several new groups of biologically interested isobenzofurans and isoindolines with labdanoid substitution. The structure of all new compounds was proven by elemental and spectral analysis: IR, mass-, and NMR data.Results: The synthesis of 15,16-dialkynyl substituted furanolabdanoids was carried out. Au(III)-Catalyzed cycloisomerization of those compounds proceeded highly selectively with the formation of optically active 4-substituted 7-hydroxy-3(6)-propargylaminomethylisobenzofurans or 7-hydroxy-3(6)-propargyloxymethylisoindolines. The cycloisomerization of the 15-(prop-2-yn-l-yloxymethyl)-16-((N-p-toluenesulfonyl)-prop2-yn-1-ylaminomethyl)labdatriene proceeded in part on the 15 position and involved the previously unknown intramolecular transfer of N-(p-toluenesulfonyl)propargylaminomethyl substituent to the oxygen in the stage of formation of an aromatic ring. A feasible reaction mechanism for this transformation is presented. It was revealed that the conversion of labdanoid furan-15-ynes to 1,3-dihydroisobenzofurans depends on the nature of the substituent in the 16 position of the furanolabdanoid.Conclusions: The present study sheds light on the Au(III)-catalyzed cycloisomerization of new group of highly functionalized furandialkynes. Also, new groups of alkynyloxymethyl or alkynylaminomethyl substituted optically active isobenzofurans and isoindolines were obtained and fully characterized.

KW - Diterpenoids

KW - dialkynes

KW - isoindolines

KW - isobenzofurans

KW - gold catalysis

KW - cycloisomerization

KW - ACTIVE PLANT METABOLITES

KW - SYNTHETIC TRANSFORMATIONS

KW - MACROHETEROCYCLIC COMPOUNDS

KW - ACID

KW - YNE

KW - DITERPENOIDS

KW - Isoindolines

KW - Gold catalysis

KW - Dialkynes

KW - Isobenzofurans

KW - Cycloisomerization

UR - http://www.scopus.com/inward/record.url?scp=85059990022&partnerID=8YFLogxK

U2 - 10.2174/1570179415666180918160421

DO - 10.2174/1570179415666180918160421

M3 - Article

VL - 15

SP - 1147

EP - 1153

JO - Current Organic Synthesis

JF - Current Organic Synthesis

SN - 1570-1794

IS - 8

ER -