【正文】 issued regulations for the preparation of drugs analogous to the WHO rules，and it applies these strictly. Exports of drugs to the USA，like those of finished products，require regular inspection of the production facilities by the FDA. 5 It may merely be noted here that such careful control applies not only to the products， but also to the raw materials (control of starting Materials)，and also to the intermediates. Clearly. the technical and hygienic equipment of the production and the storage areas have to fulfill set conditions. Since only a few pounds，such as acetylsalicylic acid，paracetamol and vitamins，are prepared in large amounts，most of the actual production takes place in multipurpose (multiproduct) facilities. .Special care has to be taken to avoid crosscontamination by other products what can be effected by good cleansing of used apparatus. A careful description and definition of all stored intermediates and products is needed.Selected from H. J. Roth and A. Kleemann, Pharmaceutical Chemistry, Vol. 1，Drug Synthesis, Ellis Horwood Limited，England, 1988.長期以來，美國藥品管理局，美國食品和藥物管理局（FDA）已發(fā)出的藥品制劑類似于誰的規(guī)則規(guī)定，而且適用于這些嚴格。它們構成的質量有關的藥品生產證書互認的生產和檢驗的基礎。良好生產規(guī)范39。號567,1975，附件1A）。1969年，世界衛(wèi)生組織發(fā)表了`保障藥品質量的論文中（WHO技術報告號418,1969，附錄二，附錄二是有關`適當的做法的賠償和保障藥品質量。進一步的輔助化學品包括活性炭和催化劑。No. 567，1975，Appendix 1A). This has in the meantime bee known as `Good Manufacturing Practices39。.Appendix 2 is concerned with the `Proper Practice for Reparation and Safeguarding Quality in Drugs39。在較小程度上乙醚，四氫呋喃，乙二醇醚，二甲基甲酰胺（DMF）和二甲基亞砜（DMSO）的使用在特殊的反應。除了實際的起始原料和中間體溶劑作為反應介質要求和通過再結晶純化，兩者。對于大多數的化學品是在涉及大量生產?；谶@個原因，它是在適當的地方，說明這本書的重要中間體，尤其是樹。這意味著幾乎全部領域的有機和有機金屬化學中的一部分也被覆蓋。藥物合成知識提供了寶貴的刺激研發(fā)化學家以及。按中間體和副產品代理。因此，合成路線的知識是有用的。In Table 1 it was already shown that over 75%of all pharmaceutical agents are obtained by total synthesis. Therefore knowledge of the synthetic routes is useful. Understanding also makes it possible to recognize contamination .of the agents by intermediates and by products. For the reason of effective quality control the registration authorities in many countries demand as essentials for registration a thorough documentation on the production process. Knowledge of drug syntheses provides the Ramp。胰島素酯分離，水解為人體胰島素和程序，最后由色譜純化。另一個重要進程的具體行動蛋白酶是根據申請的半合成人胰島素的生產。在這些酶可以在固定的形式使用的應用程序，在某種程度上勢必運營商 等為異構催化劑。In these applications the enzymes can be used in immobilized formssomehow bound to carriers and so used as heterogeneous catalysts. This is advantageous because they can then easily be separated from the reaction medium and recycled for further use. Another important process depending on the specific action of proteases is applied for the production of semisynthetic human insulin. This starts with pig insulin in which the alanine in the 30position of the Bchain is replaced by a threonine tertbutyl ester by the selective action of trypsin. The insulin ester is separated，hydrolyzed to human insulin and finally purified by chromatographic procedures. Sources for enzymes include not only microorganisms but also vegetable and animal materials. in化學stereospecificity和選擇性反應的酶可用于制造重要的用途。因此，含有蛋白酶制劑（如糜蛋白酶，胃蛋白酶和胰蛋白酶），淀粉酶和脂肪酶的合成主要是在與抗酸藥相結合，促進消化。隔離酶是重要的，不僅因為淀粉的酶法糖化技術重要性的今天，和葡萄糖異構果糖，他們也都在無數次試驗在診斷疾病所用的程序顯著，在酶的分析，在使用監(jiān)測治療。這個原則是有用的，尤其是在化學類固醇。 二硫鍵形成的選擇性分離后，最終由色譜凈化工序的影響。 By modern rebinant techniques microorganisms have been obtained which also allow production of peptides which were not encoded in the original genes. Modified E. coli bacteria make it thus possible to produce A and B chains of human insulin or proinsulin analogs. The disulfide bridges are formed selectively after isolation，and the final purification is effected by chromatographic procedures. In this way human insulin is obtained totally independently from any pancreatic material taken from animals. Other important peptides，hormones，and enzymes，such as human growth hormone (HGH)，neuroactive peptides，somatostatin，interferons，tissue plasminogen activator (TPA)，lymphokines，calcium regulators like calmodulin，protein vaccines，as well as monoclonal antibodies used as diagnostics，are synthesized in this way. 利用現代微生物重組技術已獲得這也讓其中不是在原來的基因編碼多肽的生產。大規(guī)模的細胞，如果不理想的產品，可進一步用作動物，由于其蛋白質含量高的飼料。在青霉素G的情況下，發(fā)酵完成200小時后，細胞的質量是由過濾分離。另外必須提供的微生物在與含氮如硫酸銨，氨水或尿素化合物生長介質，以及與無機磷酸鹽。由于更重要的發(fā)酵只發(fā)生在有氧條件下的氧氣或空氣好電源（無菌）是必要的。發(fā)酵都是在不銹鋼發(fā)酵罐出來的量高達400立方米。必須記住，但是，許多衍生工具已被用于治療使用部分合成修改。 About 5000 antibiotics have already been isolated from microorganisms，but of these only somewhat fewer than 100 are in therapeutic use. It must be remembered，however，that many derivatives have been modified by partial synthesis for therapeutic use。氨基糖苷類（如鏈霉素從灰色鏈霉菌）。頭孢菌素（頭孢枝頂）以下五組代表了美國每年170億美元的全球價值：從這些味精約35萬噸L 谷氨酸（食品添加劑）生物體和L 賴氨酸（用于植物蛋白補充）約70,000噸的生產。葡聚糖本身5萬?10萬分子量，是用作血漿代用品。二級降解產物（次生代謝物）。3。2。細胞的物質（單細胞蛋白），這兩個Eukaryonts（酵母菌和霉菌）和Prokaryonts（單細胞細菌，放線菌和）用于微生物。Over the last few years fermentation i. e. microbiological processes has bee extremely important. Through modern technology and results from genetic selection leading to the creation of high performance mutants of microorganisms，fermentation has already bee 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 obtained: 1. cell material (single cell protein)， 2. enzymes，3. primary degradation products (primary metabolites)4. secondary degradation products (secondary metabolites).在過去的幾年里發(fā)酵島大腸桿菌微生物過程變得極其重要。大腸桿菌更經濟的準備..由全合成。類固醇。一生物堿化合物。部分合成修改（半合成劑）天然產品： L 氨基酸，葡聚糖，對類固醇有針對性的修改，例如11 羥基化。一抗生素發(fā)酵。從角蛋白和明膠L 氨基酸。胰島素）從胰臟。肽激素。酶。分離（天然產物）天然來源：human insulin表1對藥物的可能性 方法舉例1。semisynthetic /3lactam antibiotics。 targeted modifications on steroids， . 11hydroxylation。Lamino acids。sera and vaccines 2. 3 Other sources一cholesterol from wool oils。cholic acid from gall。citral (intermed