药物化学实验 MEDICINAL CHEMISTRY EXPERIMENTS LI SHAO-SHUN XU DE-FENG School of Pharmacy,Shanghai Jiaotong University January 2008 0
0 药 物 化 学 实 验 MEDICINAL CHEMISTRY EXPERIMENTS LI SHAO-SHUN XU DE-FENG School of Pharmacy, Shanghai Jiaotong University January 2008
PREFACE "Experimental teaching material of medicinal chemistry"is composed according to the outline of medicinal chemistry.The purpose of this book is,through experiment,to comprehend elementary theory and knowledge of medicinal chemistry better,to grasp fundamental methods of synthesis and structural modification of drugs,to be familiar with how to design the experiment plan and how to select the experiment condition,to understand application of principle of hybridization and modern new technology and method in medicinal chemistry experiment,to standard and consolidate manipulative technology and relevant theory knowledge of organic chemistry experiment,to train students'style of integrating theory with practice,scientific attitude of seeking truth from fact and being rigorous and serious,ability of analyzing and solving actual problems,and good custom of scientific research. The characteristic of this book is adding much designing experiments to guiding experiments. It requires students to complete as independently as possible that consulting literatures,designing route and experimental manipulate.Through the training of designed experiments,whole process of scientific research is simulated.Students'consciousness of scientific research,spirit of bringing new ideas,ability of working independently and solving actual problems by theory and relevant elementary and professional knowledge of medicinal chemistry are trained.It can be the foundation of being engaged in medicine synthesis,studying new drugs and carrying out clinical medicinal chemistry. This book is the collective summary of teaching experience in department of medicinal chemistry.If there is any mistake in this book,please produce precious opinions during using it, so that we will corret and elevate when second printing or edition. School of Pharmacy Shanghai Jiaotong University 2008.1
1 PREFACE “Experimental teaching material of medicinal chemistry” is composed according to the outline of medicinal chemistry. The purpose of this book is, through experiment, to comprehend elementary theory and knowledge of medicinal chemistry better, to grasp fundamental methods of synthesis and structural modification of drugs, to be familiar with how to design the experiment plan and how to select the experiment condition, to understand application of principle of hybridization and modern new technology and method in medicinal chemistry experiment, to standard and consolidate manipulative technology and relevant theory knowledge of organic chemistry experiment, to train students’ style of integrating theory with practice, scientific attitude of seeking truth from fact and being rigorous and serious, ability of analyzing and solving actual problems, and good custom of scientific research. The characteristic of this book is adding much designing experiments to guiding experiments. It requires students to complete as independently as possible that consulting literatures, designing route and experimental manipulate. Through the training of designed experiments, whole process of scientific research is simulated. Students’ consciousness of scientific research, spirit of bringing new ideas, ability of working independently and solving actual problems by theory and relevant elementary and professional knowledge of medicinal chemistry are trained. It can be the foundation of being engaged in medicine synthesis, studying new drugs and carrying out clinical medicinal chemistry. This book is the collective summary of teaching experience in department of medicinal chemistry. If there is any mistake in this book, please produce precious opinions during using it, so that we will corret and elevate when second printing or edition. School of Pharmacy Shanghai Jiaotong University 2008.1
CATALOGUE Preface …1 General Medicinal Chemistry Labortory Rules 3 Standard Operating Procedures in the Medicinal Chemistry Labortory …4 Experimental Report… …11 Experiment Experiment 1 Preparation of Aspirin 15 Experiment 2 Preparation of Paracetamol 17 Experiment 3 Preparation of Benorylate 19 Experiment 4 Preparation of Benzocaine 21 Experiment 5 Synthesis of mandelic acid 25 Experiment 6 Preparation of Leucoacetates Shikonin 28 2
2 CATALOGUE Preface ………………………………………………………………………………… 1 General Medicinal Chemistry Labortory Rules ………………………………………… 3 Standard Operating Procedures in the Medicinal Chemistry Labortory ………… 4 Experimental Report ………………………………………………………………… 11 Experiment Experiment 1 Preparation of Aspirin …………………………………………………… 15 Experiment 2 Preparation of Paracetamol …………………………………………… 17 Experiment 3 Preparation of Benorylate ……………………………………………… 19 Experiment 4 Preparation of Benzocaine …………………………………………… 21 Experiment 5 Synthesis of mandelic acid ………………………………………… 25 Experiment 6 Preparation of Leucoacetates Shikonin …………………………… 28
GENERAL MEDICINAL CHEMISTRY LABORATORY RULES Students should come to the lab on time. Wear safety goggles.You may only remove your goggles if no one in the lab room is using chemicals or washing glassware Contact lenses must not be worn. Wear protective clothing:You should be covered from the top of your shoulder to below your knees.A laboratory coat is suitable,especially if you are not well-protected by the clothes you have chosen to wear to lab.Wear closed-toed shoes.Gloves are highly recommended at all times. Food and drink are not allowed in the lab room. You may not use personal music players(mp3,CD,tape,etc.)during your laboratory session ●No smoking Prevent chemical spills by clamping flasks containing chemicals whenever possible. Work in your hood at all times.Cover containers of compounds during transport through the lab. Prevent breakage by handling glassware with care at all times.Securely clamp reaction and vacuum flasks. Place broken glassware in the proper receptacle. Use a Bunsen burner only when directed by your TA. Place hazardous waste in the proper container. o When the fire alarm sounds,leave the building immediately. Keep a clear pathway to the exits:Do not bring your bike to lab and keep all personal items off the floor or close to the wall by the coatrack. Never conduct experiments in the laboratory alone. 3
3 GENERAL MEDICINAL CHEMISTRY LABORATORY RULES ● Students should come to the lab on time. ● Wear safety goggles. You may only remove your goggles if no one in the lab room is using chemicals or washing glassware. ● Contact lenses must not be worn. ● Wear protective clothing: You should be covered from the top of your shoulder to below your knees. A laboratory coat is suitable, especially if you are not well-protected by the clothes you have chosen to wear to lab. Wear closed-toed shoes. Gloves are highly recommended at all times. ● Food and drink are not allowed in the lab room. ● You may not use personal music players (mp3, CD, tape, etc.) during your laboratory session. ● No smoking. ● Prevent chemical spills by clamping flasks containing chemicals whenever possible. ● Work in your hood at all times. Cover containers of compounds during transport through the lab. ● Prevent breakage by handling glassware with care at all times. Securely clamp reaction and vacuum flasks. ● Place broken glassware in the proper receptacle. ● Use a Bunsen burner only when directed by your TA. ● Place hazardous waste in the proper container. ● When the fire alarm sounds, leave the building immediately. ● Keep a clear pathway to the exits: Do not bring your bike to lab and keep all personal items off the floor or close to the wall by the coatrack.. ● Never conduct experiments in the laboratory alone
STANDARD OPERATING PROCEDURES IN THE MEDICINAL CHEMISTRY LABORATORY Any student working in an unsafe manner may be dismissed from the laboratory by an instructor. 1.Attitudes and Preparation a.Come to laboratory periods on time and mentally prepared by studying the experiment and planning your activities. b.Be prepared physically;for example,don't try to do lab work on an empty stomach, or without sleep. c.Write everything you do and see in your notebook so that you can trace your actions and make corrections if necessary d.Wear sensible clothing,including shoes that are comfortable and permit rapid movement in case of emergency,and hair or hat that does not obstruct your view or dangle into the experiment. e.If you wear contact lenses,try to avoid wearing them in the lab.If you must wear contact lenses,your goggles must seal particularly well to your face. f.If you injure yourself,even slightly,report it to your instructor,who will direct you to first aid.If you experience eye irritation,flush your eyes at the nearest emergency eyewash station for 15 minutes (remove contacts)and seek medical attention immediately. g.If you have any existing physical conditions that might affect your performance,your health,or other peoples'health in the lab,please inform your instructor.This information will be kept confidential;examples might include pregnancy, medications,allergies,epilepsy,AIDS.Special arrangements may be possible. 2.Your Working Environment a.GOGGLES for chemical splash protection are required at all times in labs or instrument rooms,i.e.all parts of the lab,even when your are not handling chemicals. 4
4 STANDARD OPERATING PROCEDURES IN THE MEDICINAL CHEMISTRY LABORATORY ● Any student working in an unsafe manner may be dismissed from the laboratory by an instructor. 1. Attitudes and Preparation a. Come to laboratory periods on time and mentally prepared by studying the experiment and planning your activities. b. Be prepared physically; for example, don't try to do lab work on an empty stomach, or without sleep. c. Write everything you do and see in your notebook so that you can trace your actions and make corrections if necessary. d. Wear sensible clothing, including shoes that are comfortable and permit rapid movement in case of emergency, and hair or hat that does not obstruct your view or dangle into the experiment. e. If you wear contact lenses, try to avoid wearing them in the lab. If you must wear contact lenses, your goggles must seal particularly well to your face. f. If you injure yourself, even slightly, report it to your instructor, who will direct you to first aid. If you experience eye irritation, flush your eyes at the nearest emergency eyewash station for 15 minutes (remove contacts) and seek medical attention immediately. g. If you have any existing physical conditions that might affect your performance, your health, or other peoples' health in the lab, please inform your instructor. This information will be kept confidential; examples might include pregnancy, medications, allergies, epilepsy, AIDS. Special arrangements may be possible. 2. Your Working Environment a. GOGGLES for chemical splash protection are required at all times in labs or instrument rooms, i.e. all parts of the lab, even when your are not handling chemicals