Synthesis and evaluation of porphyrin glycoconjugates varying in linker length: preliminary effects on the photodynamic inactivation of .

Porphyrins have served as common photosensitizing agents in photomedicine due to their unique properties and broad therapeutic potential. While photodynamic therapy (PDT) offers a promising avenue for novel drug development, limitations in application due to selectivity, and the inherent hydrophobicity and poor solubility of porphyrins and other organic photosensitizers has been noted. Porphyrin glycoconjugates have recently gained attention for their potential to overcome these limitations.

Synthesis of Porphyrin and Bacteriochlorin Glycoconjugates through CuAAC Reaction Tuning.

Rapid and reproducible access to a series of unique porphyrin and bacteriochlorin glycoconjugates, including meso-glycosylated porphyrins and bacteriochlorins, and beta-glycosylated porphyrins, via copper catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) is reported for the first time. The work presented highlights the system-dependent reaction conditions required for glycosylation to porphyrins and bacteriochlorins based on the unique electronic properties of each ring system. Attenuated reaction conditions were used to synthesize fifteen new glycosylated porphyrin and bacteriochlorin analogs in 74 - 99% yield, and were extended to solid support to produce the first oligo(amidoamine)-based porphyrin glycoconjugate.

Stereoselective Intramolecular Cyclopropanation of α-Diazoacetates via Co(II)-Based Metalloradical Catalysis.

Co(II) complexes of -symmetric chiral porphyrins have been proven to be effective metalloradical catalysts for the asymmetric intramolecular cyclopropanation of allyl α-diazoacetates. 4-(Dimethylamino)pyridine (DMAP), through positive effect, plays an important role in the enhancement of the asymmetric induction for the intramolecular cyclopropanation process. This metalloradical catalytic system is suitable for cyclopropanation of allyl α-diazoacetates with varied functional groups and substitution patterns, producing bicyclic products with complete diastereocontrol and good enantiocontrol.

Highly asymmetric intramolecular cyclopropanation of acceptor-substituted diazoacetates by Co(II)-based metalloradical catalysis: iterative approach for development of new-generation catalysts.

3,5-Di(t)Bu-QingPhyrin, a new D(2)-symmetric chiral porphyrin derived from a chiral cyclopropanecarboxamide containing two contiguous stereocenters, has been developed using an iterative approach based on Co(II)-catalyzed asymmetric cyclopropanation of alkenes. The Co(II) complex of 3,5-Di(t)Bu-QingPhyrin, [Co(P2)], has proved to be a general and effective catalyst for asymmetric intramolecular cyclopropanation of various allylic diazoacetates (especially including those with α-acceptor substituents) in high yields with excellent stereoselectivities. The [Co(P2)]-based intramolecular metalloradical cyclopropanation provides convenient access to densely functionalized 3-oxabicyclo[3.

Photocurrent generation from porphyrin/fullerene complexes assembled in a tethered lipid bilayer.

A modular photocurrent generation system, based on amphiphilic porphyrin and fullerene species assembled in a tethered lipid bilayer matrix, is reported here. The key findings are (1) the amount of photoactive species can be quantitatively controlled in each leaflet of the bilayer and (2) the sequential formation of the bilayer allows a directional organization of these agents on electrodes. Photocurrent generation from seven differently configured photoactive bilayers is studied, which reveals several critical factors in achieving efficient photoinduced electron transfer across lipid membranes.

Highly asymmetric cobalt-catalyzed aziridination of alkenes with trichloroethoxysulfonyl azide (TcesN3).

A Co(II)-based catalytic system has been developed for asymmetric aziridination of alkenes with trichloroethoxysulfonyl azide (TcesN3) under mild conditions, forming the corresponding N-Tces-aziridines in high yields and excellent enantioselectivities.

Asymmetric Co(II)-catalyzed cyclopropanation with succinimidyl diazoacetate: general synthesis of chiral cyclopropyl carboxamides.

[Co(P1)] is an effective catalyst for asymmetric cyclopropanation with succinimidyl diazoacetate. The Co(II)-catalyzed reaction is suitable for various olefins, providing the desired cyclopropane succinimidyl esters in high yields and excellent diastereo- and enantioselectivity. The resulting enantioenriched cyclopropane succinimidyl esters can serve as convenient synthons for the general synthesis of optically active cyclopropyl carboxamides.

Cobalt-catalyzed asymmetric olefin aziridination with diphenylphosphoryl azide.

The cobalt(II) complexes of D2-symmetric chiral porphyrins, such as 3,5-Di(t)Bu-ChenPhyrin P5, can catalyze asymmetric olefin aziridination with diphenylphosphoryl azide (DPPA) as a nitrene source. Acceptable asymmetric inductions were observed for the [Co(P5)]-based catalytic system, forming the desired N-phosphorus-substituted aziridines in moderate to high yields and good enantioselectivities.

Synthesis of diporphyrins via palladium-catalyzed C-O bond formation: effective access to chiral diporphyrins.

Diporphyrins can be efficiently synthesized from bromoporphyrin precursors via palladium-catalyzed C-O bond formation. The synthetic methodology is general and can be applied to various diols, forming a series of homo-diporphyrins containing different types of spacers in high to excellent yields. Chiral diporphyrins can be readily constructed through the use of optically active diols.

A highly effective cobalt catalyst for olefin aziridination with azides: hydrogen bonding guided catalyst design.

[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene intermediate, is a highly active aziridination catalyst with azides. [Co(P1)] can effectively aziridinate various aromatic olefins with arylsulfonyl azides under mild conditions, forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of cobalt and the wide accessibility of arylsulfonyl azides.

Cobalt-catalyzed asymmetric cyclopropanation with diazosulfones: rigidification and polarization of ligand chiral environment via hydrogen bonding and cyclization.

A new D2-symmetric chiral porphyrin P6 (2,6-DiMeO-ZhuPhyrin) with enhanced chiral rigidity and polarity was designed and synthesized through incorporation of hydrogen bonding and cyclic structure. Its cobalt(II) complex [Co(P6)] is a highly active and selective catalyst for asymmetric cyclopropanation of alkenes with diazosulfones. The [Co(P6)]-based catalytic system is suitable for various aromatic olefins as well as electron-deficient olefins, including alpha,beta-unsaturated esters, ketones, and nitriles, forming the corresponding cyclopropyl sulfones under mild conditions in high yields and high selectivities.

Cobalt-catalyzed intermolecular C-H amination with bromamine-T as nitrene source.

Cobalt, supported by porphyrin ligands, is capable of catalyzing intermolecular nitrene insertion of sp(3) C-H bonds with bromamine-T as the nitrene source, forming the desired tosyl-protected amines with NaBr as the by-product.

Synthesis of beta-functionalized porphyrins via palladium-catalyzed carbon-heteroatom bond formations: expedient entry into beta-chiral porphyrins.

A procedure was developed for the preparation of beta-monobromo-tetraphenylporphyrin (BrTPP) in a greatly improved yield from the selective bromination of tetraphenylporphyrin (TPP) by NBS. BrTPP was successfully employed as a versatile synthon for convenient synthesis of a wide range of beta-monofunctionalized porphyrins with various heteroatom functionalities via palladium-mediated carbon-heteroatom bond formations. Examples include beta-amino, -amido, -oxo, and -mercaptoporphyrins from reactions with amines, amides, alcohols, and thiols, respectively.

Cobalt-catalyzed intramolecular C-H amination with arylsulfonyl azides.

Cobalt complexes of porphyrins are effective catalysts for intramolecular C-H amination with arylsulfonyl azides. The cobalt-catalyzed process can proceed efficiently under mild and neutral conditions in low catalyst loading without the need of other reagents or additives, generating nitrogen gas as the only byproduct. The catalytic system can be applied to primary, secondary, and tertiary C-H bonds and is suitable for a broad range of arylsulfonyl azides, leading to high-yielding syntheses of various benzosultams.