Synthetic Chlorins Bearing Auxochromes at the 3- and 13-Positions

Abstract

Synthetic chlorins bearing diverse auxochromes at the 3- and 13-positions of the macrocycle are valuable targets given their resemblance to chlorophylls a and b, which bear 3-vinyl and 13-keto groups. A de novo route has been exploited to construct nine zinc chlorins bearing substituents at the 3- and 13-positions and two benchmark zinc chlorins lacking such substituents. The chlorins are sterically uncongested and bear (1) a geminal dimethyl group in the reduced pyrroline ring, (2) a H, an acetyl, a triisopropylsilylethynyl (TIPS-ethynyl), or a vinyl at the 3-position, (3) a H, an acetyl, or TIPS-ethynyl at the 13-position, and (4) a H or a mesityl at the 10-position. The synthesis of the 13-substituted chlorins relied on p-TsOH x H2O-catalyzed condensation of an 8,9-dibromo-1-formyldipyrromethane (eastern half) and 2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin (western half), followed by metal-mediated oxidative cyclization, affording the 13-bromochlorin. Similar use of a bromo- or TIPS-ethynyl-substituted western half provided access to 3-substituted chlorins. A 3-bromo, 13-bromo, or 3,13-dibromochlorin was further transformed by Pd-coupling to introduce the vinyl group (via tributylvinyltin), TIPS-ethynyl group (via TIPS-acetylene), or acetyl group (via tributyl(1-ethoxyvinyl)tin, followed by acidic hydrolysis). In the 10-mesityl-substituted zinc chlorins, the series of substituents, 3-vinyl, 13-TIPS-ethynyl, 3-TIPS-ethynyl, 13-acetyl, 3,13-bis(TIPS-ethynyl), 3-TIPS-ethynyl-13-acetyl, or 3,13-diacetyl, progressively causes (1) a redshift in the absorption maximum of the B band (405-436 nm) and the Q(y) band (606-662 nm), (2) a relative increase in the intensity of the Q(y) band (I(B)/I(Q) = 4.2-1.5), and (3) an increase in the fluorescence quantum yield phi(f) (0.059-0.29). The zinc chlorins bearing a 3-TIPS-ethynyl-13-acetyl or a 3,13-diacetyl group exhibit a number of spectral properties resembling those of chlorophyll a or its zinc analogue. Taken together, this study provides access to finely tuned chlorins for spectroscopic studies and diverse applications.

Singlet Oxygen in a Cell: Spatially Dependent Lifetimes and Quenching Rate Constants

“…Chlorin was synthesized as previously described. 31,32 Instrumentation. Details of the instrumentation and approach used in this study are provided elsewhere.…”

Synthesis of hydrodipyrrins tailored for reactivity at the 1- and 9-positions

“…The synthesis of the corresponding tetrahydrodipyrrin-imidate (14) is shown in Scheme 4. The Michael addition of 9 18 with methyl 3,3-dimethylacrylate (10b) was examined under several conditions.…”

“…Although chlorophylls and bacteriochlorophylls lack the geminal dialkyl motif, synthetic analogues that contain a geminal dialkyl group in the pyrroline ring exhibit characteristic chlorin or bacteriochlorin features and are quite stable compounds. [10][11][12][13][14][15] The de novo syntheses that we developed of chlorins, which drew heavily on methods established in the total synthesis of bonellin, 16,17 are shown in Scheme 1. Each de novo synthesis involves the convergent joining of an Eastern half and a Western half.…”

“…10-13 A related synthesis uses a formyl-containing Eastern half (3b) to give the fully unsubstituted zinc chlorin 4b. 14 The de novo synthesis of bacteriochlorins is shown in Scheme 2. A dihydrodipyrrin bearing an acetal moiety (5) undergoes self-condensation under acidic conditions at room temperature.…”

Synthesis and Matrix Metalloproteinase-12 Inhibitory Activity of Ageladine A Analogs

“…41c was prepared according to the reported method. 17) Thus, protection of 55 18) , 56 19) , 58a-c, 20) and 59 21) with a SEM group provided 41a, d, g, i, n, and 60, respectively. The aldehyde 41a was further converted to 41f by the regioselective Suzuki-Miyaura cross-coupling reaction following the procedure reported by Handy and Sabatini.…”