Remarkable Regioselective Position-10 Bromination of Bacteriopyropheophorbide-a and Ring-B Reduced Pyropheophorbide-a

Abstract

Both bacteriopyropheophorbide-a and ring-B reduced pyropheophorbide-a on reacting with NBS (N-bromosuccinamide) undergo electrophilic bromination to provide 10-bromo analogs. The electronic nature of the substituents present at position-3 did not make any difference in regioselective outcome of the brominated products. These relatively stable brominated chlorins and bacteriochlorins provide an easy way of introducing a wide variety of functionalities, which could be extremely useful in developing improved agents for biomedical applications and supramolecular chemistry.

meso‐ and β‐Pyrrole‐Linked Chlorin‐Bacteriochlorin Dyads for Promoting Far‐Red FRET and Singlet Oxygen Production

“…Two different synthetic strategies were followed for the preparation of Chl–Bchl dyads with a diphenyl linkage (Scheme 1) or with an ester linkage (Scheme 2). For synthesis of the unsymmetrical dyads 7 and 8 , methyl 3‐acetyl bacteriopyropheophorbide 1 was obtained from Rhodobacter sphaeroides , [16] which on reacting with N ‐bromosuccinimide (NBS) gave the corresponding 10‐bromo analogue 3 in 66 % yield by following our previously reported methodology [17] . The chlorins 2 [methyl‐3‐(1′‐hexyloxy)ethyl‐3‐devinylpyropheophorbide‐a] [18] and 2 a [methyl‐3‐ethyl‐3‐devinylpyropheo phorbide‐a], differing only in the functional group at position‐3, were reacted individually with pyridinium tribromide to give the respective 20‐bromo analogues 4 and 5 , which were isolated in 87 % yield [17] .…”

“…For synthesis of the unsymmetrical dyads 7 and 8 , methyl 3‐acetyl bacteriopyropheophorbide 1 was obtained from Rhodobacter sphaeroides , [16] which on reacting with N ‐bromosuccinimide (NBS) gave the corresponding 10‐bromo analogue 3 in 66 % yield by following our previously reported methodology [17] . The chlorins 2 [methyl‐3‐(1′‐hexyloxy)ethyl‐3‐devinylpyropheophorbide‐a] [18] and 2 a [methyl‐3‐ethyl‐3‐devinylpyropheo phorbide‐a], differing only in the functional group at position‐3, were reacted individually with pyridinium tribromide to give the respective 20‐bromo analogues 4 and 5 , which were isolated in 87 % yield [17] . Reaction of the 10‐bromobacteriochlorin 3 with the 20‐bromo chlorins 4 and 5 in presence 6 under Suzuki reaction conditions [19, 20] afforded the desired Chl–Bchl dyads 7 and 8 in 41 and 46 %, yield, respectively, along with the debrominated analogues 1 , 2 , and 2 a in 30–35 % yield (Scheme 1).…”

Regioselective Synthesis and Photophysical and Electrochemical Studies of 20‐Substituted Cyanine Dye–Purpurinimide Conjugates: Incorporation of NiII into the Conjugate Enhances its Tumor‐Uptake and Fluorescence‐Imaging Ability

“…An in vivo biological investigation indicated that aside from the overall lipophilicity, the position of the substituents in the tetrapyrrolic skeleton also plays a crucial role in the long-term PDT response. [30] This report shows the utility of the Suzuki reaction [31] in synthesizing such candidates by introducing an additional functionality into the photosensitizer and their application in developing efficient agents for fluorescence imaging with and without PDT. [20][21][22] Photosensitizers with high tumor avidity are also being used as vehicles to deliver the desired imaging agents (radionuclides for nuclear imaging, fluorophores for optical-imaging agents, Gd III chelates for MR imaging) to the target site.…”

“…[29] For quite some time, our laboratory has also been interested in developing an efficient method for the regioselective synthesis of 20-meso-substituted purpurinimides, which could be utilized for developing a variety of photosensitizers (cationic, anionic, and targeted analogues) and bifunctional agents ( Figure 2). [30] This report shows the utility of the Suzuki reaction [31] in synthesizing such candidates by introducing an additional functionality into the photosensitizer and their application in developing efficient agents for fluorescence imaging with and without PDT. The regioselective introduction of a variety of substituents at the 20-meso-postion by the Suzuki reaction also provides an opportunity to alter the overall lipophilicity and target specificity of the molecule(s) by varying the nature of the substitution.…”

The Structures of Gd(III) Chelates Conjugated at the Periphery of 3‐(1’‐Hexyloxy)ethyl‐3‐devinylpyropheophorbide‐a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

“…The intermediate tricarboxylic analog was reacted with gadolinium chloride (GdCl 3 ), and the conjugate 4 was isolated in 86 % yield. For introducing the Gd chelates at position‐20, HPPH methyl ester was first reacted with pyridinium bromide following our own methodology and afforded the corresponding 20‐bromo analog [23] . It was further reacted with 3‐( tert ‐butoxycarbonyl)phenylboronic acid pinacol ester under Suzuki reaction conditions and the intermediate 20‐benzoic acid derivative 2 was obtained in good yield after treating the intermediate with TFA.…”