Synthesis of meso-substituted chlorins via tetrahydrobilene-a intermediates.
Synthesis of meso-substituted chlorins via tetrahydrobilene-a intermediates.
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通过四氢胆烯-a 中间体合成内消旋二氢卟酚。
DOI：
10.1021/jo0104835
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Lindsey,JS
中科院分区：
文献类型：
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作者：
Taniguchi,M;Ra,D;Mo,G;Balasubramanian,T;Lindsey,JS
在还原环中包含双二甲基的氯构建块和在大环周围以特定模式的合成手柄有望在仿生和材料化学中发挥作用。先前的方法是将二氢二吡啶（西半部分）和溴代吡咯烷-单甲醇（东半部分）缩合，然后将假定的二氢二烯-氧化环化，以产率约10%的速度生成中位取代的氯化锌。二氢双吡啶的有限稳定性阻碍了氯生成过程的研究。我们现在已经改进了这个方法。合成了一个四氢二吡啶的西半部分（2,3,4,5-四氢-1,3,3-三甲基二吡啶），并发现它是相当稳定的。在含有100 mM TFA的CH3CN中，西半部和东半部（各100 mM）在室温下顺利冷凝30 min。得到的线性四吡咯，2,3,4,5-四氢二烯-a，也很稳定，可以用来研究转化为氯的过程。氧化环化的精细条件包括：四氢二烯-a（10 mM）、AgTf（3 - 5摩尔当量）、Zn(OAc)2（15摩尔当量）和2,2,6,6-四甲基哌啶（15摩尔当量）在CH3CN中回流暴露于空气中4 - 6小时，产生氯化锌。形成氯的过程可以在两个烧瓶过程或一个烧瓶过程中实施。采用双烧瓶法制备六种含锌氯基取代基，如五氟苯基、3,5-二叔丁基苯基、tms -苯甲酸乙酯、碘苯基或乙基苯基（在氧化环化过程中发生了tms -乙基的脱保护）。分离得到的缩合和氧化环化反应的分步产率分别为32−72%和27−62%，使得东、西两部分的总产率分别为12−45%。综上所述，引入的改进使100毫克数量的氯构建块能够以一种简单而合理的方式制备。
Chlorin building blocks incorporating a geminal dimethyl group in the reduced ring and synthetic handles in specific patterns at the perimeter of the macrocycle are expected to have utility in biomimetic and materials chemistry. A prior route employed condensation of a dihydrodipyrrin (Western half) and a bromodipyrromethane-monocarbinol (Eastern half), followed by oxidative cyclization of the putative dihydrobilene-ato form the meso-substituted zinc chlorin in yields of ∼10%. The limited stability of the dihydrodipyrrin precluded study of the chlorin-forming process. We now have refined this methodology. A tetrahydrodipyrrin Western half (2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin) has been synthesized and found to be quite stable. The condensation of the Western half and an Eastern half (100 mM each) proceeded smoothly in CH3CN containing 100 mM TFA at room temperature for 30 min. The resulting linear tetrapyrrole, a 2,3,4,5-tetrahydrobilene-a, also is quite stable, enabling study of the conversion to chlorin. Refined conditions for the oxidative cyclization were found to include the following: the tetrahydrobilene-a(10 mM), AgTf (3−5 molar equiv), Zn(OAc)2(15 molar equiv), and 2,2,6,6-tetramethylpiperidine (15 molar equiv) in CH3CN at reflux exposed to air for 4−6 h, affording the zinc chlorin. The chlorin-forming process could be implemented in either a two-flask process or a one-flask process. The two-flask process was applied to form six zinc chlorins bearing substituents such as pentafluorophenyl, 3,5-di-tert-butylphenyl, TMS-ethyl benzoate, iodophenyl, or ethynylphenyl (deprotection of the TMS-ethynyl group occurred during the oxidative cyclization process). The stepwise yields (isolated) for the condensation and oxidative cyclization processes forming the tetrahydrobilene and zinc chlorin were 32−72% and 27−62%, respectively, giving overall yields of zinc chlorin from the Eastern and Western halves of 12−45%. Taken together, the refinements introduced enable 100-mg quantities of chlorin building blocks to be prepared in a facile and rational manner.