Synthesis Of A-mesyloxy Ketones And 17-oxazolyl-androstane Derivatives By Gold-catalyzed Of Alkyne

Homogeneous gold catalysis has been in-depth researched in recent years,and a lot of valuable results have been achieved.Au(I)cation and its complexes are rather unique soft Lewis and ? acids,which can be uesd as catalyst for the activation of C-C multibonds toward various types of reactions,such as nucleophilic reactions,oxidative coupling reactions and Diels-Aider reactions.a-Oxo gold carbene is a kind of important reactive intermediates in homogeneous gold catalysis,which can be generated from inter-and intramolecular oxidation of alkynes by nucleophilic oxidants.For example,pyridine/quinoline N-oxides,nitro,nitrone,amine N-oxide,sulfoxide and epoxide et.al oxidants.On many occasions,a-oxo gold carbene can replace hazardous a-diazo carbonyl compounds undergo various reactions,such as can undergo nucleophilic attack by imine,aromatics,alkanes,leading to cascade reactions and the construction of new C-C,C-N,C-O,C-S bond skeletones.This thesis is concerned with studies on the synthesis of carbonyl compounds and five-membered nitrogen-and oxygen-containing heterocycles by gold-catalyzed intermolecular oxidation of terminal alkynes generated a-oxo gold carbene intermediates.Besides,a series of steroid derivatives were synthesized using gold catalysis methodology for the design of biologically active steroid nucleus.It is divided into two parts as follows:1.A general solution for the synthesis of various a-mesyloxy ketones has been developed by gold-catalyzed oxidation of alkyne.We have examined the impact of the catalyst and oxidant respectively by establised a model reaction using phenylacetylene as the substate,and obtained the optimum reaction conditions.With 5 mol%Cy3PAuNTf2 catalyst,1.1 equiv MsOH,1.3 equiv 3,5-dichloropyridine N-oxide dissolved in chlorobenzene and react under room temperatrue for 8 hours,the mixture was concentrated and the residue was purified by chromatography on silica gel.Mechanistically,reactive a-oxo gold carbenes is generated as intermediates through intermolecular oxidation of alkynes and subsequent intermolecular O-H insertion with methanesulfonic acid.This safe and efficient generation of gold carbenes offers a potentially general entry into a-oxo gold carbene chemistry without using hazardous diazo ketones.2.A series of 17-(2',5'-disubstituted-oxazolyl)-androsta-4,16-dien-3-one derivatives were designed and synthesized from 4-androstene-3,17-dione.First,17-ethynyl-17-hydroxyandrost-4-en-3-one was generated by nucleophilic-addition reaction at postion C-17.Then 17-ethynyl-17-hydroxyandrost-4-en-3-one was converted to 17-ethyny landrost-4,16-dien-3-one by dehydrolysis.The target conpounds 17-(2',5'-disubstituted-oxazolyl)-androsta-4,16-dien-3-one derivatives were furnished via gold-catalyzed intermolecular oxidation of 17-ethynylandrost-4,16-dien-3-one in nitriles.The structures of the targeted compounds were characterized by 1H NMR,13C NMR,IR and HRMS.These synthesized compounds were screened for in vitro antitumor activity by MTT assay against MCF-7(human breast cancer cell line),A549(human lung cancer cell line),Bel-7402(human liver cancer cell line),Hela(human cervical cancer cell line)and PC-3M-1E8(human prostate cancer cell line).The results revealed that the tested compounds showed significant antitumor activities and all tested compounds displayed higher selectivity against MCF-7 cell line.