Chemical Structural Modification of Tanshinone Compounds and Synthesis of Halogenated

Intermediate
Author :FanCuiPing
Tutor:YinWeiPing
School :Henan University of Science and Technology
CLC :TQ460.1
TYPE :Masters thesis
Download the PDF Full Text:http://www.topresearch.org/showinfo-238-681902-0.html
Year:2013
Abstract:
Tanshinone compounds, the fat-soluble substances of Traditional ChineseMedicine dan shen, have
been widely used in medical field. However, the poor water-solubility has greatly limited its
application for a long time. In medicinal chemistry,chemical modification of natural products structure
plays a crucial role in therapeuticimprovement and drug development. This study targets the
cardiovascular compounds,tanshinons, tanshinoneA, tanshinoneI and1,2-dehydro tanshinoneA to
transformand modify structures. The proposed products are expected to exhibit improved
watersolubility and thus effectively function in halogenated reaction series.The traditional method to
improve the water solubility is the introduction of polargroups in the drug structure. However, it is
difficult to carry out such structuralmodification in tanshinones-like ring. Over the years, lots of work
have been done totransform the tanshinone from fat-soluble to water-soluble. A critical key is to
choosean appropriate structure change which can release the parent drug under
physiologicalconditions and also improve the transport and metabolism of drugs
(therefore,bioavailability) according to requirement of body tissues. Moreover, the polarityadjustment
by introducing polar groups in the tanshinones and thebiological/pharmacological activity
improvement of tanshinone derivatives are widelyaccepted and employed by the current research,
such as the preparation of Chlorinatedtanshinone. The study investigated the mechanisms of
tanshinones halogenatedreaction; chemical transformation; synthesis of a series of tanshinone
halogenatedcompounds and its intermediate; and synthesis of tanshinone compounds. Through aseries
of iodine of tanshinone compounds synthesized in the generation and bromide,the best conditions of
tanshinones halogenated reaction were determined by IR, NMR;product intermediates and single
crystal diffraction methods were tested and structureswere characterized.Tanshinone compounds
iodination. The study used tanshinoneA as raw material, halogenation reagent with potassium iodide
and iodate formed by reaction in glacialacetic acid; research ratio on the reaction solvent, reaction
time, reaction temperatureand tanshinoneA and iodine quantity were discussed, and the optimum
reactionconditions were determined as follows: glacial acetic acid was solvent, the ratio of
rawmaterials n (tanshinoneA):n (potassium iodide):n (potassium iodate)=10:10.5:7,reaction was
performed at80for an hour, TLC test until the material pointdisappeared means the end point of the
reaction, the reaction then can be terminated.Tanshinones bromination. Through the comparison of the
two synthetizedmethods of1,16-dibromine tanshinoneA, the optimum reaction conditions
weredetermined as follows: dichloromethane was used as solvent, benzoyl peroxide (BPO)was
initiator, reaction temperature was40, tanshinone brominated compoundswere as high as75%or
above yield. Synthesis of1,16-dibromine tanshinone II A,the yield was75%;16-bromination of
tanshinone, the yield reached83%.Though its difficult to modify the anshinone structure,
introducing activity ofhalogenated groups of intermediates and further implementation of polar
groupssubstituted strategies are the purpose of the present study. All tanshinone iodo cantherefore
stably synthesize with high yield. It has been realized as tanshinones polarwater soluble intermediates
of molecular compound transformation.