Mild and scalable synthesis of phosphonorhodamines.
Mild and scalable synthesis of phosphonorhodamines.
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DOI：
10.1039/d3sc02590j
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发表时间：
2023-10-25
期刊：
影响因子：
8.4
通讯作者：
Miller, Evan W.
中科院分区：
文献类型：
--
作者：
Turnbull, Joshua L.;Golden, Ryan P.;Benlian, Brittany R.;Henn, Katharine M.;Lipman, Soren M.;Miller, Evan W.
自1887年被发现以来，罗丹明已成为生物成像中不可或缺的荧光团。近年来的研究广泛探索了10′位置的杂原子取代和3′、6′氮上的各种取代模式。虽然3-羧基罗丹明和3-磺基罗丹明在19世纪首次被报道，但3-膦类似物从未被报道过。在这里，我们报告了一个温和的，可扩展的合成路线3-磷酸甘胺。我们探索底物范围和研究外源无酸缩合的机理细节。四甲基-3-磷膦胺（phosTMR）衍生物可以在1.5 mmol的规模上以高达98%的收率（2步）获得。与3-羧基和3-磺代氨基衍生物相比，phosTMR的水溶性提高了12至500倍，并具有优异的化学稳定性。此外，磷酸盐允许化学衍生化；磷酸酯mr的酯化促进了与3-羧基罗丹明不同的定位谱的细胞内递送。游离膦酸盐可以被纳入分子线支架中，以产生膦化罗丹明电压报告因子，phosphonoRhoVR。PhosRhoVR 1只需6步合成，总产率为37%，可提供bb0 400mg的材料，而先前报道的RhoVR 1的产率为6步，约2%。PhosRhoVR 1具有优异的电压灵敏度（37% ΔF/F），与RhoVR 1相比，细胞亮度增加了2倍。在19世纪首次报道，罗丹明已经成为生物成像不可或缺的荧光团。我们报道了一个新的，高收率的合成水溶性罗丹明与膦酸代替传统的羧酸盐。
Since their discovery in 1887, rhodamines have become indispensable fluorophores for biological imaging. Recent studies have extensively explored heteroatom substitution at the 10′ position and a variety of substitution patterns on the 3′,6′ nitrogens. Although 3-carboxy- and 3-sulfono-rhodamines were first reported in the 19th century, the 3-phosphono analogues have never been reported. Here, we report a mild, scalable synthetic route to 3-phosphonorhodamines. We explore the substrate scope and investigate mechanistic details of an exogenous acid-free condensation. Tetramethyl-3-phosphonorhodamine (phosTMR) derivatives can be accessed on the 1.5 mmol scale in up to 98% yield (2 steps). phosTMR shows a 12- to 500-fold increase in water solubility relative to 3-carboxy and 3-sulfonorhodamine derivatives and has excellent chemical stability. Additionally, phosphonates allow for chemical derivatization; esterification of phosTMR facilitates intracellular delivery with localization profiles that differ from 3-carboxyrhodamines. The free phosphonate can be incorporated into a molecular wire scaffold to create a phosphonated rhodamine voltage reporter, phosphonoRhoVR. PhosRhoVR 1 can be synthesized in just 6 steps, with an overall yield of 37% to provide >400 mg of material, compared to a 6-step, ∼2% yield for the previously reported RhoVR 1. PhosRhoVR 1 possesses excellent voltage sensitivity (37% ΔF/F) and a 2-fold increase in cellular brightness compared to RhoVR 1. First reported in the 1800s, rhodamines have become indispensable fluorophores for biological imaging. We report a new, high-yielding synthesis of water soluble-rhodamines with a phosphonic acid instead of the traditional carboxylate.
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影响因子：
5.2
作者：
Dwight, Stephen J.;Levin, Sergiy
通讯作者：
Levin, Sergiy
影响因子：
16.6
作者：
Fischer, Christian;Sparr, Christof
通讯作者：
Sparr, Christof
DOI：
10.1039/jr9510001024
发表时间：
1951-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY
影响因子：
--
作者：
KNOTT, EB
通讯作者：
KNOTT, EB
DOI：
10.1073/pnas.77.2.990
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
JOHNSON, LV;WALSH, ML;CHEN, LB
通讯作者：
CHEN, LB
影响因子：
18.2
作者：
Grimm JB;Brown TA;Tkachuk AN;Lavis LD
通讯作者：
Lavis LD