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1、Unit 1 Production of DrugsDepending on their production or origin pharmaceutical agents can be split into three groups:I .Totally synthetic materials (synthetics)，.Natural products，and .Products from partial syntheses (semi-synthetic products).The emphasis of the present book is on the most importan
2、t compounds of groups I and 一thus Drug synthesis. This does not mean，however，that natural products or other agents are less important. They can serve as valuable lead structures，and they are frequently needed as starting materials or as intermediates for important synthetic products.Table 1 gives an
3、 overview of the different methods for obtaining pharmaceutical agents.1单元生产的药品 其生产或出身不同药剂可以分为三类：1。完全（合成纤维）合成材料，。天然产物，和 。产品从（半合成产品）的部分合成。本书的重点是团体的最重要的化合物和一所以药物合成。这并不意味着，但是，天然产品或其他代理人并不太重要。它们可以作为有价值的领导结构，他们常常为原料，或作为重要的合成中间体产品的需要。表1给出了获取药剂的不同方法的概述。Table 1 Possibilities for the preparation of drugsMeth
4、ods Examples1. Total synthesis -over 75 % of all pharmaceutical agents (synthetics)2. Isolation from natural sources (natural products): 2.Plants -alkaloids;enzymes;heart glycosides;polysaccharides;tocopherol; steroid precursors (diosgenin, sitosterin);citral (intermediate product for vitamins A, E，
5、and K) 2.2 Animal organs一enzymes;peptide hormones;cholic acid from gall; insulin) from the pancreas;sera and vaccines 2. 3 Other sources一cholesterol from wool oils;L-amino acids from keratin and gelatine hydrolysates3. Fermentation一antibiotics;L-amino acids;dextran; targeted modifications on steroid
6、s， e.g. 11-hydroxylation; also insulin, interferon, antibodies, peptide hormones，enzymes，vaccines4. Partial synthetic modification of natural products (semisynthetic agents) 一 alkaloid compounds;semisynthetic /3-lactam antibiotics;steroids;human insulin表1对药物的可能性 方法举例1。全合成，超过75的药剂（合成纤维）2。分离（天然产物）天然来源
7、：2.1植物-生物碱;酶;心甙，多糖，维生素E;类固醇前体（薯蓣皂素，sitosterin），柠檬醛（中间产品维生素A，E，K）2.2动物器官一酶;肽激素;胆酸从胆;胰岛素）从胰脏;血清疫苗2。从角蛋白和明胶L -氨基酸;三一胆固醇从羊毛油脂的其他来源水解3。一抗生素发酵;L -氨基酸，葡聚糖，对类固醇有针对性的修改，例如11 -羟基化;也胰岛素，干扰素，抗体，肽激素，酶，疫苗4。部分合成修改（半合成剂）天然产品： 一生物碱化合物;半合成/ 3-内酰胺类抗生素;类固醇;人胰岛素Several therapeutically significant natural products which
8、were originally obtained from natural sources are today more effectively -i. e. more economically -prepared. by total synthesis. Such examples include L-amino acids，Chloramphenicol，Caffeine, Dopamine， Epinephrine，Levodopa, peptide hormones，Prostaglandins，D-Penicillamine，Vincamine， and practically al
9、l vitamins.其中几个重要的治疗作用最初是从天然产品天然来源获得更有效的今天，我。大肠杆菌更经济的准备.由全合成。这样的例子包括L-氨基酸，氯霉素，咖啡因，多巴胺，肾上腺素，左旋多巴，肽类激素，前列腺素，D -青霉胺，长春胺，以及几乎所有的维生素。Over the last few years fermentation - i. e. microbiological processes has become extremely important. Through modern technology and results from genetic selection leading
10、to the creation of high performance mutants of microorganisms，fermentation has already become the method of choice for a wide range of substances. Both Eukaryonts (yeasts and moulds)and Prokaryonts(single bacterial cells，and actinomycetes)are used microorganisms. The following product types can be o
11、btained: 1. cell material (single cell protein)， 2. enzymes，3. primary degradation products (primary metabolites)4. secondary degradation products (secondary metabolites).在过去的几年里发酵-岛大肠杆菌微生物过程变得极其重要。通过现代技术和基因选择的结果导致了突变体的微生物创造高性能，发酵，已成为首选方法各种各样的物质。这两个Eukaryonts（酵母菌和霉菌）和Prokaryonts（单细胞细菌，放线菌和）用于微生物。下列产
12、品类型可以得到：1。细胞的物质（单细胞蛋白），2。酶，3。主要降解产物（主要代谢物），4。二级降解产物（次生代谢物）。 Disregarding the production of dextran from the mucous membranes of certain microorganisms，e. g. Leuconostoc mesenteroides，classes 2 and 3 are the relevant ones for the preparation of drugs. Dextran itself，with a molecular weight of 50,000
13、100,000，is used as a blood plasma substitute. Among the primary metabolites the L-amino acids from mutants of Corynebacterium glutamicum and Brevibacterium flavum are especially interesting. From these organisms some 350，000 tones of monosodium L-glutamate (food additive)and some 70，000 tones of L-l
14、ysine(supplement for vegetable proteins)are produced. Further important primary metabolites are the purina nucleotides，organic acids， lactic acid，citric acid，and vitamins，for example vitamin B,2 from Propionibacterium shermanii.Among the secondary metabolites the antibiotics must be mentioned first.
15、 The following five groups represent a yearly worldwide value of US-$17 billion:不顾来自某些微生物，大肠杆菌粘膜生产的葡聚糖克明串珠mesenteroides，2和3级是毒品有关的准备工作。葡聚糖本身5万10万分子量，是用作血浆代用品。其中主要来自谷氨酸棒杆菌代谢产物和黄色短杆菌突变体的L -氨基酸特别有趣。从这些味精约35万吨L -谷氨酸（食品添加剂）生物体和L -赖氨酸（用于植物蛋白补充）约70,000吨的生产。此外重要的初级代谢产物的普瑞纳核苷酸，有机酸，乳酸，柠檬酸和维生素，例如维生素B，从丙酸shermanii 2。其中次生代谢产物的抗生素必须首先提到。以下五组代表了美国每年170亿美元的全球价值： penicillins ( Penicillium chrysogenum )， cephalosporins ( Cephalosporium acremonium )， tetracyclines ( Streptomyces aureofaciens )， erythromycins ( Streptomyces erythreus )， aminoglycosides (e. g. streptomycin from Streptomyces griseus
