Homogeneous Catalytic Functionalization of the Steroidal Framework

Szteránvázas vegyületek homogénkatalitikus funkcionalizálása

Kiss Mercédesz

Kémia Doktori Iskola

Deli József

Kálai Tamás

Nagy Géza

Balogh János

Wölfling János

Kollár László

Pécsi Tudományegyetem

2015-10-06T12:50:15Z

2015-10-06T12:50:15Z

2015-10-06

Természettudományok - Natural sciences

homogénkatalízis

szteránváz

funkcionalizálás

palládium-katalizálás

aminokarbonilezés

homogenous-catalytism

steroidal functionalization

aminocarbonylation

Using palladium-catalyzed homogeneous aminocarbonylation as a key reaction 3,17-dicarboxamido-androst-3,5,16-triene and 3,17-dicarboxamido-androst-2,4,16-triene derivatives possessing various amide moieties were synthesized under mild reaction conditions such as atmospheric carbon monoxide pressure and 50 °C. Compounds containing 3-iodo-3,5-diene, 3-iodo-2,4-diene and 17-iodo-5,16-diene structural motifs were used in the aminocarbonylation and the N-nucleophiles were varied systematically. Three amines, such as tert-butylamine, piperidine and methyl alaninate were used as N-nucleophiles in the aminocarbonylation. All variations of 3,17-dicarboxamides were synthesized using this methodology. A set of new steroid dimers linked through ring A-ring A or ring D-ring D was synthesized under relatively harsh conditions, such as high carbon monoxide pressure and 100 °C, using palladium-catalyzed homogeneous aminocarbonylation. Compounds containing 3-iodo-3,5-diene, 3-iodo-2,4-diene and 17-iodo-5,16-diene functionalities were used in the aminocarbonylation and four diamines, such as 1,2-diaminoethane, 1,4-diaminobutane, 1,4-diaminobenzene and (1S,2S)-(+)-1,2-diaminocyclohexane were used as N-nucleophiles. Androst-4-ene-3,17-dion was used as a starting material for the iodoalkene derivatives above. The synthetic strategy of the multistep synthesis was based on the consecutive use of three types of reactions: (i) the protection/deprotection of one of the keto functionalities (3-one or 17-one) as ethylene ketals, (ii) the transformation of the other keto group to iodoalkene functionality via its hydrazone, and (iii) palladium-catalyzed aminocarbonylation of the iodoalkene functionality.

99

angol

PhD

http://pea.lib.pte.hu/handle/pea/11721