TOTAL SYNTHESIS OF PRODIGIOSIN, PRODIGIOSENE, AND DESMETHOXYPRODIGIOSIN - DIELS-ALDER REACTIONS OF HETEROCYCLIC AZADIENES AND DEVELOPMENT OF AN EFFECTIVE PALLADIUM(II)-PROMOTED 2,2'-BIPYRROLE COUPLING PROCEDURE
TOTAL SYNTHESIS OF PRODIGIOSIN, PRODIGIOSENE, AND DESMETHOXYPRODIGIOSIN - DIELS-ALDER REACTIONS OF HETEROCYCLIC AZADIENES AND DEVELOPMENT OF AN EFFECTIVE PALLADIUM(II)-PROMOTED 2,2'-BIPYRROLE COUPLING PROCEDURE
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DOI：
10.1021/jo00242a013
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发表时间：
1988-04-01
影响因子：
3.6
通讯作者：
PATEL, M
中科院分区：
文献类型：
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作者：
BOGER, DL;PATEL, M
蛋白质（1）的总合成是一种从锯齿状铜霉菌中分离出来的红色色素，具有一类现有的息肉基吡咯的Chrocteristic吡咯基吡乙烯骨骼骨骼，具有抗菌和细胞毒性特性。该方法是基于二甲基1,2,4,5-四嗪-3,6-二羧酸二甲基二甲基的逆电子需求双向反应的应用。 1,2-二嗪.fwdarw。制备prodigiosin吡罗尔环B的吡咯策略以及随后实施有效的分子内钯（II）促进的2,2'' - 日记偶联以构建Prodigiosin 2,2''' - 双吡咯AB环系统。原位产生的吡咯-1-羧酸的活化酯衍生物或使用吡咯-1-羧酸酸酐，被证明适合于生成混合1,1'' - 羧基氯吡咯化合物，用于钯（II）含有的混合混合混合混合物，2,2'' - 旁皮耦合。详细介绍了这种方法的扩展，以制备天然存在的吡咯吡咯甲苯，prodigiosene（2a）和2-甲基-3-五苯基生殖基因（2e，desmethoxyprodigiosin）。报道了Protigioiosin（1），prodigiosene（2a）和2-甲基-3-五苯基普罗酮（2E）的体外细胞毒性特性的比较，并揭示了异常的细胞毒性效力（3.7.Times。10-4.mu.g/ g/ g/ g/ g/ g/ g/ g/ g/ g/ ML = 3.7。可能归因于存在Protigiosin C-6甲氧基取代基的存在。
The total synthesis of prodigiosin (1), a red pigment first isolated from Serratia marcescens, possessing the chracteristic pyrrolylpyrromethene skeleton of a class of occurring polypyrroles exhibiting antimicrobial and cytotoxic properties, is detailed. The approach is based on the application of an inverse electron demand Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate in a 1,2,4,5-tetrazine .fwdarw. 1,2-diazine .fwdarw. pyrrole strategy for preparation of prodigiosin pyrrole ring B and the subsequent implementation of an effective intramolecular palladium(II)-promoted 2,2''-diaryl coupling for construction of the prodigiosin 2,2''-bipyrrole AB ring system. In situ generated activated ester derivatives of pyrrole-1-carboxylic acid or the use of pyrrole-1-carboxylic acid anhydride proved suitable for the generation of mixed 1,1''-carboxnylpyrrole compounds for use in the palladium(II)-promoted mixed, 2,2''-bypyrrole coupling. Extensions of this approach to the preparation of the naturally occurring parent pyrrolylpyrromethene, prodigiosene (2a), and 2-methyl-3-pentylprodigiosene (2e, desmethoxyprodigiosin) are detailed. A comparison of the in vitro cytotoxic properties of prodigiosin (1), prodigiosene (2a), and 2-methyl-3-pentylprodigiosene (2e) are reported and reveal exceptional cytotoxic potency (3.7 .times. 10-4 .mu.g/mL = 3.7 .times. 10-10 g/mL) for prodigiosin against 9PS (P388) mouse leukemia which may be attributed to the presence of the prodigiosin C-6 methoxy substituent.