Study of conditions for streamlined assembly of a model bacteriochlorophyll from two dihydrodipyrrin halves
Study of conditions for streamlined assembly of a model bacteriochlorophyll from two dihydrodipyrrin halves
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DOI：
10.1039/d0nj04855k
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发表时间：
2021-01-14
影响因子：
3.3
通讯作者：
Lindsey, Jonathan S.
中科院分区：
文献类型：
--
作者：
Nguyen, Khiem Chau;Wang, Pengzhi;Lindsey, Jonathan S.
一个长期目标是获得天然光合细菌叶绿素的合成途径。最近开发的路线需要AD二氢二吡咯（I，带有连接到吡咯啉环D的甲醛）和BC二氢二吡咯（II，带有连接到吡咯环C的β-酮酯）的Knoevenagel缩合以形成Z/E-烯酮。E-烯酮III-E的酸介导的双环闭合（Nazarov环化、亲电芳族取代和甲醇消除）提供了细菌叶绿素骨架BC-1，其含有异环（环E）、环D中的反式二烷基基团和环B中的偕二甲基基团。先前的工作建立了合成和完整的反式二烷基基团和菌绿素生色团。这里的对应报告涉及的双环封闭条件的深入研究：催化剂/溶剂调查;网格搜索，包括时间过程中的[III-E]与[酸]浓度强调等摩尔，反摩尔，和可变酸线的调查;和二氢卟酚副产物定量。结果表明：（1）双环闭合反应可以在4 h内完成（t（1/2）约为40 min），而不是20 h，得到约1/5的二氢卟酚副产物（0.16%），同时保持BC-1的产率（高达77%）;（2）III的单独的Z/E-烯酮具有相当的反应性;（3）亚化学计量量的酸是无效的;（4）Knoevenagel缩合（40 mM，室温，哌啶/乙酸的乙腈溶液）和酸介导的双环闭合（0.20 mM，80 ℃，Yb（OTf）（3）的乙腈溶液）可以在两步法中进行;和（5）锌插入形成ZnBC-1是直接的。总之，这些结果使二氢二吡啉反应物转化为细菌叶绿素模型化合物成为可能。
A long-term goal is to gain synthetic access to native photosynthetic bacteriochlorophylls. A recently developed route entails Knoevenagel condensation of an AD dihydrodipyrrin (I, bearing a carboxaldehyde attached to pyrroline ring D) and a BC dihydrodipyrrin (II, bearing a beta-ketoester attached to pyrrole ring C) to form the Z/E-enone. Acid-mediated double-ring closure of the E-enone III-E (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol) affords the bacteriochlorophyll skeleton BC-1 containing the isocyclic ring (ring E), a trans-dialkyl group in ring D, and a gem-dimethyl group in ring B. Prior work established the synthesis and the integrity of the resulting trans-dialkyl groups and bacteriochlorin chromophore. The counterpart report here concerns an in-depth study of conditions for the double-ring closure: catalyst/solvent surveys; grid search including time courses of [III-E] versus [acid] concentrations emphasizing equimolar, inverse molar, and variable acid lines of inquiry; and chlorin byproduct quantitation. Key findings are that (1) the double-ring closure can be carried out in 4 h (t(1/2) similar to 40 min) instead of 20 h, affording similar to 1/5th the chlorin byproduct (0.16%) while maintaining the yield of BC-1 (up to 77%); (2) the separate Z/E-enones of III have comparable reactivity; (3) sub-stoichiometric quantities of acid are ineffective; (4) the Knoevenagel condensation (40 mM, room temperature, piperidine/acetic acid in acetonitrile) and the acid-mediated double-ring closure (0.20 mM, 80 degrees C, Yb(OTf)(3) in acetonitrile) can be carried out in a two-step process; and (5) zinc insertion to form ZnBC-1 is straightforward. Together, the results enable streamlined conversion of dihydrodipyrrin reactants to the bacteriochlorophyll model compounds.