第五节前列腺素类似物 Prostanoic Acid Prostaglandins or Prostanoids 为一族有二十碳的多不饱和脂肪酸衍生物。 of them is seven carbon atom 155-POA: 15-cp/PGAg 5member ring 案例 Prostaglandins(PGs) of the 灭的直捷因压下降休克教死时 冲的江管属植物 增加133倍。 Prostaglandins(PGs) Prostaglandins(PGs) aT enl e chai and C15. A.B.C.D.E and F depending aistry of the C9 hydroxy grou 3 3 135 第五节 前列腺素类似物 为一族有二十碳的多不饱和脂肪酸衍生物. Prostaglandins or Prostanoids O H OH CO2H 1 8 10 O H OH CO2H 1 8 10 15S-PGA2 15-epi-PGA2 15S 15R Weinheimer, A.J.; Spraggins, R.L. Tetrahedron Lett. 1969, 5185-5188. The first PGs compounds isolated from Florida Coral by Weinheimer in 1969. 136 Chemically Prostaglandins are C20 carboxylic acids consisting of a five member ring with two side chains. One of them is seven carbon atoms and the other of eight carbon atoms. All prostaglandins may be regarded as derivative of Prostanoic Acid, a trivial name. 7 carbon side chain 5 member ring 8 carbon side chain Prostanoic Acid 2 COOH 3 4 5 6 7 8 9 10 11 12 13 14 15 1 16 17 18 19 20 137 1993年 10月日本横滨发生一起食江篱属(Gracilaria verrucosa)海洋植物中毒的事件，中毒2 人，死亡1人。迄今 在日本已知的江篱属植物中毒已有3起，死3人。几起中毒的 共同特点是：(1)采集不久即生吃，(2)主要症状为呕吐、嗳 气、腹泻等，死亡的直接原因是血压下降导致休克，致死时 间一般在十几小时，(3)死者均为女性。同期从神奈川县野岛 冲的江篱属植物中检出前列腺素(PGE2)，含量最高达78.6 mg/kg。同时发现，当在该植物中加入花生四烯酸(Na盐)时， 其PGE2的含量会在数分钟后增加1.3~3倍。极微量PGE2即可 引起子宫收缩，短时间内大量生成的PGE2会对女性产生极强 的作用，这可能是该物质主要导致女性中毒的重要原因。 案 例 138 Prostaglandins and related molecules are called eicosanoids as a class. The term eicosanoid is derived from “eicosa” meaning “twenty”, referring to the 20 carbons in most of the molecules. The eicosanoids are used as signaling molecules. They generally act locally, either affecting cell that makes them or nearby cells; in most cases, eicosanoids are not systemic hormones, because of their short half-lives. Most prostaglandins are synthesized from arachidonic acid (20:4△5,8,11,14). These are called “Series 2” products, because most have two double bonds. However, the triene fatty acid 20:3 △8,11,14 can also be used; the products have one fewer double bond than the arachidonic acid derivatives and are called Series 1 products. Prostaglandins (PGs) 139 Prostaglandins are a family of important chemicals involved in a variety of biological regulatory functions and are found in most biological tissues. The name is derived from the fact that the original members of the series were derived from the prostate gland (in sheep). Structurally, they are a C20 system containing a cyclopentane unit, a carboxylic acid functional group and -OH groups at C11 and C15. They are divided into series A, B, C, D, E and F depending on the cyclopentane substituents. They are biosynthesised is from C20 fatty acids, such as arachidonic acid, which in turn are formed from linoleic acid. Prostaglandins (PGs) 140 The stereochemistry of substituents on 5-member cyclopentane ring could be a or b. The configuration of C-15 hydroxyl function is 15(S). Naturally occurring prostaglandins could be divided into nine groups (A-I) based on the substitution pattern on the cyclopentane ring. Individual member of each group is distinguished by the number of double bonds in the side chain which are denoted by the subscript 1, 2, 3. In the F-series, a further subscript is added to define the stereochemistry of the C9 hydroxy group. Prostaglandins (PGs) CO2H O H H 1 8 10 HO PGE1 15