Synthesis of model bacteriochlorophylls containing substituents of native rings A, C and E
Synthesis of model bacteriochlorophylls containing substituents of native rings A, C and E
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DOI：
10.1039/d1nj02469h
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发表时间：
2021-07-08
影响因子：
3.3
通讯作者：
Lindsey, Jonathan S.
中科院分区：
文献类型：
--
作者：
Chung, Duy T. M.;Tran, Phuong Vy;Lindsey, Jonathan S.
正在开发的细菌叶绿素a及其类似物的合成路线依赖于通过Knovenagel缩合然后双环闭合(纳扎罗夫环化、亲电芳香取代和消除甲醇)来连接AD-二氢二氢吡咯(含D-环甲醛)和BC-二氢二吡咯(含C-环β-酮酯基和B-环二甲氧基甲基)。以前的合成研究给出了细菌叶绿素骨架，在B环上含有一个宝石-二甲基，在D环上有一个反式二烷基，在A环的3位上有一个碳乙氧基。为了探索天然取代基的引入，合成了两个细菌叶绿素类似物，一个带有12-甲基和3-甲氧基，另一个带有2，12-二甲基和3-乙酰基。在Knovenagel反应中，12-甲基导致了一半的产率(与未取代类似物相比)，但在所有其他步骤中，包括双环闭合的速率和产率，影响不显著，尽管已知烷基有助于吡咯的亲电取代。然而，2-甲基-3-乙酰基在几个步骤中导致产率降低，包括Knovenagel反应，但不是双环闭合。结果表明，在完全合成天然色素的道路上存在障碍和缺口。
A route under development for the synthesis of bacteriochlorophyll a and analogues relies on joining an AD-dihydrodipyrrin (bearing a D-ring carboxaldehyde) and a BC-dihydrodipyrrin (bearing a C-ring beta-ketoester group and a B-ring dimethoxymethyl group) via Knoevenagel condensation followed by double-ring closure (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol). Prior synthetic studies afforded the bacteriochlorophyll skeleton containing a gem-dimethyl group in ring B, a trans-dialkyl group in ring D, and a carboethoxy group at the 3-position of ring A. To explore the incorporation of native substituents, the synthesis of two bacteriochlorophyll analogues thereof was pursued, one with 12-methyl and 3-carboethoxy groups and the other with 2,12-dimethyl and 3-acetyl groups. The 12-methyl group resulted in half the yield (versus the unsubstituted analogue) in the Knoevenagel reaction, but insignificant effects in all other steps including the rate and yield of double-ring closure despite the known effects of alkyl groups to facilitate electrophilic substitution of pyrroles. The 2-methyl-3-acetyl group, however, resulted in diminished yields in several steps, including the Knoevenagel reaction, but not the double-ring closure. The results point to obstacles and openings on the path to total syntheses of the native pigments.