Elaboration of an unexplored substitution site in synthetic bacteriochlorins

Zhang, Nuonuo; Reddy, Kanumuri Ramesh; Jiang, Jianbing; Taniguchi, Masahiko; Sommer, Roger D.; Lindsey, Jonathan S.

doi:10.1142/s1088424615500534

Cited by 6 publications

(6 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The chief synthetic routes to bacteriochlorins entail (1) semisynthesis beginning with bacteriochlorophylls, , (2) reduction of or cycloaddition with porphyrins, , and (3) de novo syntheses. The de novo syntheses to date include the total synthesis of tolyporphin A as the diacetate (R = Ac, Chart ) by Kishi and co-workers, − and a synthesis of non-natural bacteriochlorins that we − and others − have been developing. The latter route is shown in Scheme .…”

Section: Introductionmentioning

confidence: 99%

“…The synthesis shown in Scheme has proved quite versatile for incorporation of diverse β-pyrrole substituents but is limited for the introduction of substituents at the meso- and the β-pyrroline positions. To date, the meso-substituents include alkoxy (methoxy, 2-hydroxyethoxy) at the 5-position and entities (e.g., carbonyl, aryl, ethynyl) that can be introduced at the 15-position via Pd-mediated coupling of the 5-alkoxy-15-bromobacteriochlorin (Chart , panel A). Examples include BC-1 and BC-2 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Northern–Southern Route to Synthetic Bacteriochlorins

Liu

Lindsey

2016

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

A new route to bacteriochlorins via Northern-Southern (N-S) self-condensation of a dihydrodipyrrin-acetal complements a prior Eastern-Western (E-W) route. Each bacteriochlorin was prepared in five steps from an α-halopyrrole and a 2,2-dimethylpent-4-ynoic acid. The first three steps follow Jacobi's synthesis of dihydrodipyrrins: Pd-mediated coupling to form a lactone-pyrrole, Petasis reagent treatment for methenylation, and Paal-Knorr type ring closure to form the 1,2,2-trimethyl-substituted dihydrodipyrrin. Subsequent steps entail conversion of the 1-methyl group to the 1-(dimethoxymethyl) unit and acid-catalyzed self-condensation of the resulting dihydrodipyrrin-acetal. The essential differences between the N-S and E-W routes lie in (1) the location of the gem-dimethyl group (with respect to the 1-acetal unit) at the 2- versus 3-position in the dihydrodipyrrin-acetals, respectively, (2) the method of synthesis of the dihydrodipyrrins, and consequently (3) access to diverse substituted bacteriochlorins including those with substituents at the meso-positions. Ten new bacteriochlorins bearing 0-6 total aryl, alkyl, and carboethoxy substituents at the β-pyrrole and/or meso-positions have been prepared, with yields of macrocycle formation of up to 39%. Four single-crystal X-ray structures (two intermediates, two bacteriochlorins) were determined. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Q band in the region 713-760 nm.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Northern–Southern Route to Synthetic Bacteriochlorins

Liu

Lindsey

2016

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Purification by a 3-column chromatographic approach [ 33 ] including adsorption chromatography, size-exclusion chromatography (SEC), and adsorption chromatography again (to remove materials that leach from the SEC resin) afforded H 2 C9-PEG 6 in 88% yield for the two synthetic steps. Suzuki coupling partner 6 was prepared by reaction [ 34 ] of 2-(4-aminophenyl)-1,3-dioxa-4,4,5,5-tetramethylborolane and succinic anhydride. Pd-mediated Suzuki coupling [ 35 , 36 ] of H 2 C9-PEG 6 and 6 yielded target bioconjugatable PEGylated chlorin H 2 C10-PEG 6 in 74% yield.…”

Section: Resultsmentioning

confidence: 99%

“…4-Oxo-4-[(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino]butanoic acid ( 6 ). Following a reported procedure [ 34 ], a solution of 5 (100 mg, 0.456 mmol) in CHCl 3 (18.7 mL) was treated with succinic anhydride (49.7 mg, 0.497 mmol), the resulting mixture was stirred at room temperature for 4 h. Then the mixture was diluted with ethyl acetate, washed with brine, dried (Na 2 SO 4 ) and concentrated to afford a light yellow solid (142 mg, 98%): 1 H-NMR (CDCl 3 , 300 MHz, the CO 2 H and amide NH proton peaks were not observed) δ 7.76 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 2.79–2.77 (m, 2H), 2.73–2.62 (m, 2H), 1.33 (s, 12H); 13 C-NMR (CD 3 OD, 100 MHz) δ 175.0, 171.5, 141.4, 135.2, 118.5, 83.6, 48.1, 47.9, 47.7, 47.5, 47.3, 31.1, 28.6, 23.9, 23.7; ESI-MS obsd 320.1660 [M + H] + , calcd 320.1664 (M = C 16 H 22 BNO 5 ).…”

Section: Methodsmentioning

confidence: 99%

Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and Studies in Aqueous Media

Liu

Hood

et al. 2018

Molecules

View full text Add to dashboard Cite

Fluorophores that absorb and emit in the red spectral region (600–700 nm) are of great interest in photochemistry and photomedicine. Eight new target chlorins (and 19 new chlorins altogether)—analogues of chlorophyll—of different polarities have been designed and synthesized for various applications; seven of the chlorins are equipped with a bioconjugatable tether. Hydrophobic or amphiphilic chlorins in a non-polar organic solvent (toluene), polar organic solvent (DMF), and aqueous or aqueous micellar media show a sharp emission band in the red region and modest fluorescence quantum yield (Φf = 0.2–0.3). A Poisson analysis implies most micelles are empty and few contain >1 chlorin. Water-soluble chlorins each bearing three PEG (oligoethyleneglycol) groups exhibit narrow emission bands (full-width-at-half maximum <25 nm). The lifetime of the lowest singlet excited state and the corresponding yields and rate constants for depopulation pathways (fluorescence, intersystem crossing, internal conversion) are generally little affected by the PEG groups or dissolution in aqueous or organic media. A set of chlorin–avidin conjugates revealed a 2-fold increase in Φf with increased average chlorin/avidin ratio (2.3–12). In summary, the chlorins of various polarities described herein are well suited as red-emitting fluorophores for applications in aqueous or organic media.

show abstract

“…The reaction of 1 under the standard mild conditions (TMSOTf and 2,6-di- tert -butylpyridine (DTBP) in CH 2 Cl 2 at room temperature) afforded bacteriochlorin in 41% yield [ 37 ] (consistent with 30%–46% under other conditions [ 18 , 31 ]). The oxocarbenium ion 1a is a likely species in the head-to-tail dimerization process ( Scheme 2 ) [ 33 , 38 ], although the extent to which the pyrrole participates in resonance-stabilization of the 1-oxocarbenium ion 1b has remained unclear. Attempts to employ a dihydrodipyrrin bearing a single alkoxy substituent at the 1-methyl position ( 2 , R = Me; 3 , R = Ph) under identical catalysis conditions (TMSOTf, DTBP in CH 2 Cl 2 ) met with failure to form the bacteriochlorin (0% yield), which we attributed to the inability to form ( 2 , 3-i ) or adequately stabilize ( 2 , 3-ii ) the 1° carbenium ion [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including Insights into Essential Motifs of their Hydrodipyrrin Precursors

et al. 2017

Self Cite

View full text Add to dashboard Cite

Synthetic bacteriochlorins—analogues of bacteriochlorophylls, Nature’s near-infrared absorbers—are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin–carbinol or dihydrodipyrrin–acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline ring to ensure stability toward oxidation. The two routes differ in the location of the gem-dimethyl group at the respective 3- or 2-position in the dihydrodipyrrin, and the method of synthesis of the dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1-carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1-(aryl)carbinol, and upon subsequent acetylation, the corresponding dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin–acetate). Self-condensation of the dihydrodipyrrin–acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2-dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case, the aromatization process entails a 2e−/2H+ (aerobic) dehydrogenative oxidation following the dihydrodipyrrin self-condensation. Comparison of a tetrahydrodipyrrin–acetal (0%) versus a dihydrodipyrrin–acetal (41%) in bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins revealed the importance of resonance stabilization of the reactive hydrodipyrrin intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins have been prepared. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 726–743 nm.

show abstract

Elaboration of an unexplored substitution site in synthetic bacteriochlorins

Cited by 6 publications

References 74 publications

Northern–Southern Route to Synthetic Bacteriochlorins

Northern–Southern Route to Synthetic Bacteriochlorins

Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and Studies in Aqueous Media

Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including Insights into Essential Motifs of their Hydrodipyrrin Precursors

Contact Info

Product

Resources

About