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1、Unit 1 Production of Drugs Depending 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 import
2、ant 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 give
3、s an 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 preparatio
4、n of drugs Methods Examples 1. Total synthesis -over 75 % of all pharmaceutical agents (synthetics) 2. Isolation from natural sources (natural products):2.1 Plants -alkaloids;enzymes;heart glycosides;polysaccharides;tocopherol;steroid precursors (diosgenin, sitosterin);citral (intermediate product f
5、orvitamins A, E，and K)2.2 Animal organs 一 enzymes;peptide hormones;cholic acid from gall; insulin) from thepancreas;sera and vaccines2. 3 Other sources 一 cholesterol from wool oils;L-amino acids from keratin and gelatinehydrolysates3. Fermentation 一 antibiotics;L-amino acids;dextran; targeted modifi
6、cations on steroids，e.g. 11-hydroxylation; also insulin, interferon, antibodies, peptidehormones，enzymes，vaccines 4. Partial synthetic modification of natural products (semisynthetic agents):一 alkaloid compounds;semisynthetic /3-lactam antibiotics;steroids;human insulin表 1 对药物的可能性准备 方法举例 1。全合成，超过 75
7、的药剂（合成纤维） 2。分离（天然产物）天然来源：2.1 植物-生物碱;酶;心甙，多糖，维生素 E;类固醇的前体（薯蓣皂素，sitosterin） ，柠檬醛（中间产品维生素 A，E 和 K）2.2 动物器官一酶;肽激素;胆酸从胆;胰岛素）从胰脏;血清和疫苗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 therapeu
8、tically significant natural products which 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-
9、Penicillamine，Vincamine， and practically all 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 technol
10、ogy and results from genetic selection leading 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 micro
11、organisms. The following product types can be obtained: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 Eu
12、karyonts（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.
13、 Dextran itself，with a molecular weight of 50,000 100,000，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-glu
14、tamate (food additive)and some 70，000 tones of L-lysine(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 m
15、etabolites the antibiotics must be mentioned first. 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
16、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)
