Expanded Scope of Synthetic Bacteriochlorins via Improved Acid Catalysis Conditions and Diverse Dihydrodipyrrin-Acetals

Abstract

Bacteriochlorins are attractive candidates for a wide variety of photochemical studies owing to their strong absorption in the near-infrared spectral region. The prior acid-catalysis conditions [BF(3) x O(Et)(2) in CH(3)CN at room temperature] for self-condensation of a dihydrodipyrrin-acetal (bearing a geminal dimethyl group in the pyrroline ring) typically afforded a mixture of three macrocycles: the expected 5-methoxybacteriochlorin (MeOBC-type), a 5-unsubstituted bacteriochlorin (HBC-type), and a free base B,D-tetradehydrocorrin (TDC-type). Here, a broad survey of >20 acids identified four promising acid catalysis conditions of which TMSOTf/2,6-di-tert-butylpyridine in CH(2)Cl(2) at room temperature was most attractive owing to formation of the 5-methoxybacteriochlorin as the sole macrocycle regardless of the pyrrolic substituents in the dihydrodipyrrin-acetal (electron-withdrawing, electron-donating, or no substituent). Eleven new dihydrodipyrrin-acetals were prepared following standard routes. Application of the new acid catalysis conditions has afforded diverse bacteriochlorins (e.g., bearing alkyl/ester, aryl/ester, diester, and no substituents) in a few days from commercially available starting materials. Consideration of the synthetic steps and yields for formation of the dihydrodipyrrin-acetal and bacteriochlorin underpins evaluation of synthetic plans for early installation of bacteriochlorin substituents via the dihydrodipyrrin-acetal versus late installation via derivatization of beta-bromobacteriochlorins. Treatment of the 5-methoxybacteriochlorins with NBS gave regioselective 15-bromination when no pyrrolic substituents were present or when each pyrrole contained two substituents; on the other hand, the presence of a beta-ethoxycarbonyl group caused loss of regioselectivity. The 15 new bacteriochlorins prepared herein exhibit a long-wavelength absorption band in the range 707-759 nm, providing tunable access to the near-infrared region. Taken together, this study expands the scope of available bacteriochlorins for fundamental studies and diverse applications.

(Metallo)porphyrins as Potent Phototoxic Anti‐Cancer Agents after Irradiation with Red Light

“…In addition, additive effects of performing PDT with subtherapeutic concentrations of cisplatin could be observed. Our approach is a synthetically simple alteration to current research directions for modified porphyrin analogues, such as porphycene [30] or chlorin [31] compounds. [1] Porphyrins 2 and 4 showed a phototoxic behaviour that can be explained by the evolution of singlet oxygen derived from the spectral properties in the range of 550-680 nm.…”

Amphiphilic BODIPY-Hydroporphyrin Energy Transfer Arrays with Broadly Tunable Absorption and Deep Red/Near-Infrared Emission in Aqueous Micelles

“…Known compounds: 1 , 38 C-Br , 48 BC-P , 3 BC-Br 2 , 49 BC-E , 50 C-COOH , 7 BDP-4 , 7 and BDP-F , 7 were prepared following reported procedures.…”

[8π+2π] Cycloaddition of meso‐Tetra‐ and 5,15‐Diarylporphyrins: Synthesis and Photophysical Characterization of Stable Chlorins and Bacteriochlorins

“…One strategy to minimize these problems is the dialkyl geminal β-substituted bacteriochlorins approach proposed by Lindsey, where dehydrogenation is blocked. [5] However, a simpler way to produce chlorins or bacteriochlorins is through Diels-Alder and 1,3-dipolar cycloadditions.…”