Syntheses of biological active natural products having highly alkylated piperazine ring

最近，从放线菌和海洋生物中分离出几种天然存在的异喹啉醌类抗生素。这种抗生素的独特结构，加上它们巨大的生物活性，给合成化学家带来了巨大的挑战。我们的基本计划包括使用2，5-哌嗪二酮来构建具有高度烷基化哌嗪环的该目标的基本骨架。本文的目的是概述我们在实现这一具有挑战性的目标方面所采取的一般方法和取得的进展。1）<plus-minus>以（Z）-1-乙酰基-3-芳叉基-6-（芳甲基）-2，5-哌嗪二酮为起始原料，经19步全合成了（Z）-沙夫霉素B。2)本文分离出三个沙夫霉素类抗生素的次要组分：沙夫霉素F、G、H，并通过与天然产物和沙夫霉素B全合成中间体的光谱数据比较，确定了它们的结构。3)1-甲基-3-（2，4，5-三甲氧基-3-甲基苯甲基）-2，5-哌嗪二酮的有效合成，它被证明是制备1，5-亚氨基-3-苯并氮杂环辛衍生物（番红霉素的右半部分）的有用中间体。4)通过改进的Pictet-Spengler反应，包括刘易斯酸介导的O，N-缩醛环化反应，温和有效地合成了1，2，3，4-四氢异喹啉。该反应通过制备沙弗拉霉素左半部分的基本骨架来证明。5)介绍了异喹啉类抗生素沙夫霉素A的合成方法。6)用氧化硒将9-甲氧基-3，8，11-三甲氧基-4-氧代-1，2，3，4，5，6-六氢-1，5-亚氨基-3-苯并氮杂辛-7，10-二酮氧化成相应的6-羟基化合物。这是一个很好的方法，使saframycin C和D从saframycin B。7)介绍了雷那霉素A的合成方法和雷那霉素的结构修正

Recently several naturally occurring isoquinolinequinone antibiotics have been isolated from Actinomycetes and from marine organisms. The unique structure of this antibiotics, coupled with their great biological activities, offers a formidable challenge to the synthetic chemist. Our basic plan involves the use of the 2,5-piperazinediones to construct the basic skeleton of this target having highly alkylated piperazine ring. The purpose of this paper is outline the general approach and progress that we have made toward this challenging target. The results are summarized as followed:1) We succeed in a 19-step total synthesis of (<plus-minus>)-saframycin B from (Z)-1-acetyl-3-arylidene-6-(arylmethyl)-2,5-piperazinedione. 2) Three minor components of safiamycin group antibiotics, saframycins F, G, H were isolated and their structure were determined by comparison with the spectral data of natural products and the intermediates of a total synthesis of saframycin B. 3) An efficient synthesis of 1-methyl-3-(2,4,5-trimethoxy-3-methylphenylmethyl)-2,5-piperazinedione, which is shown to be a useful intermediate for preparation of the 1,5-imino-3-benzazocine derivative (right half of safraniycins). 4) A mild and efficient method for the synthesis of 1,2,3,4-tetrahydioisoquinolines by a modified Pictet-Spengler reaction involving Lewis acid-mediated cyclization of the O, N-acetals. This reaction is demonstrated with a preparation of the basic skeleton of the left half of saframycins. 5) A synthetic strategy for the preparation of isoquinoline antibiotic, saframycin A is outlined. 6) 9-Methoxy-3,8,11-trimeth-oxy-4-oxo-1,2,3,4,5,6-hexahydro-1,5-imino-3-benzazocin-7,10-dione is oxidized to the corresponding 6-hydroxy compound with selenium oxide. This is a good way to make saframycins C and D from saframycin B. 7) Synthetic approach of renieramycin A and a revised structure for renieramycins are presente