Synthesis of AD-Dihydrodipyrrins Equipped with Latent Substituents of Native Chlorophylls and Bacteriochlorophylls
Synthesis of AD-Dihydrodipyrrins Equipped with Latent Substituents of Native Chlorophylls and Bacteriochlorophylls
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带有天然叶绿素和细菌叶绿素潜在取代基的 AD-二氢二吡林的合成
DOI：
10.1021/acs.joc.1c01239
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Lindsey, Jonathan S.
中科院分区：
文献类型：
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作者：
Wang, Pengzhi;Lindsey, Jonathan S.
天然叶绿素和细菌叶绿素共享一个共同的反式取代的吡咯啉环D（17-丙酸，18-甲基），而多样性发生在环A，特别是在3-位。合成了两个具有天然D环取代基和可调控A环取代基的二氢二吡咯。该合成依赖于Schreiber修饰的Nicholas反应来构建立体化学定义的环D的前体，二烷基取代的α-4-炔酸。完整的丙酸的羧酸基团被证明是不可行的，于是研究了保护的丙酸酯（− CO2 tBu）和几种潜在的丙基醚。叔丁基二苯基甲硅烷基保护的丙醇取代基被证明对于手性N-酰化恶唑烷酮的反应是令人满意的，经过8步得到（2S，3S）-2-（3-（（叔丁基二苯基甲硅烷基）氧基）丙基）-3-甲基-4-炔酸，产率约30%。环A的两种变体，2-叔丁氧羰基-3-Br/H-5-碘-4-甲基吡咯，通过Barton-Zard路线制备。从吡咯和戊炔酸形成二氢二吡咯需要Jacobi Pd介导的内酯形成、Petasis亚甲基化和Paal-Knorr型吡咯啉形成。这两个AD-二氢二吡咯带有D-环甲基和受保护的丙醇基团，其立体化学构型与天然（细菌）叶绿素的立体化学构型相同，并且在对应于（细菌）叶绿素的3-位的环A中具有溴取代或没有取代。内酯-吡咯中间体在生成二氢二吡咯的路径上的类似β-位也被成功溴化，为（细菌）叶绿素合成的后期多样化提供了机会。
Native chlorophylls and bacteriochlorophylls share a commontrans-substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substituents and tailorable A-ring substituents have been synthesized. The synthesis relies on a Schreiber-modified Nicholas reaction to construct the stereochemically defined precursor to ring D, a dialkyl-substituted pent-4-ynoic acid. The carboxylic acid group of the intact propionic acid proved unworkable, whereupon protected propionate (−CO2tBu) and several latent propyl ethers were examined. Thetert-butyldiphenylsilyl-protected propanol substituent proved satisfactory for reaction of the chiralN-acylated oxazolidinone, affording (2S,3S)-2-(3-((tert-butyldiphenylsilyl)oxy)propyl)-3-methylpent-4-ynoic acid in ∼30% yield over 8 steps. Two variants for ring A, 2-tert-butoxycarbonyl-3-Br/H-5-iodo-4-methylpyrrole, were prepared via the Barton–Zard route. Dihydrodipyrrin formation from the pyrrole and pentynoic acid entailed Jacobi Pd-mediated lactone formation, Petasis methenylation, and Paal–Knorr-type pyrroline formation. The two AD-dihydrodipyrrins bear the D-ring methyl and protected propanol groups with a stereochemical configuration identical to that of native (bacterio)chlorophylls, and a bromine or no substitution in ring A corresponding to the 3-position of (bacterio)chlorophylls. The analogous β-position of a lactone–pyrrole intermediate on the path to the dihydrodipyrrin also was successfully brominated, opening opportunities for late-stage diversification in the synthesis of (bacterio)chlorophylls.