Bacteriochlorins synthesis

Synthesis of chlorins, bacteriochlorins, isobacteriochlorins, and higher reduced porphyrins 98PHC1. 

The extremely high sensitivity of bacteriochlorins to various reactions makes their chemistry very difficult. This might also be one reason why methods for the total synthesis of bacteriochlorins had not, until very recently, been developed.13 Total synthesis of a tolyporphin model was reported by Kishi et al.13 using an approach that is very closely related to Eschenmoser s syntheses of hexahydroporphyrins from reduced linear tetrapyrroles by cyclization (see Section 1.5.1). 

All other methods for obtaining bacteriochlorins are by partial synthesis from porphyrins, chlorins or chlorin derivatives. The bacteriochlorin is thereby produced by reactions which occur at the peripheral /J-C — C double bonds of the higher unsaturated systems. The main problem of these syntheses is the lack of regio- and stereoselectivity because three or four C —C double bonds, which are present in the starting products may be attacked, so that rcgio-and stcreoisomcric products can be formed. 

Reaction of porphyrins with nitrones has also been studied and the results obtained showed that this is a versatile approach leading to the synthesis of isoxazolidine fused-chlorins (Scheme 26). For instance, chlorin 74 was successfully prepared from the reaction of the jV-methylnitrone, generated in situ from JV-methyl hydroxylamine and paraformaldehyde, with porphyrin Id . It is important to note that bis-addition also took place, yielding exclusively bacteriochlorin type derivatives 76 and 77 (Figure 6). This result contrasts with those obtained in 1,3-DC reactions with azomethinic ylides where isobacteriochlorins were obtained preferentially. 

Bacteriochlorins, 851 Barbituric acid metal complexes, 798 Barium alkoxides synthesis, 336 Barium complexes phthalocyanines, 863 porphyrins, 820 Becium homblei copper accumulation, 964 Benzaldehyde, 2-amino-self-condensation aza macrocycles from, 900 Benzamide, o-mercapto-metal complexes, 655 Benzamide oximes metal complexes, 274 Benzamidine, /V, V -diphenyl-metal complexes. 275 Benzene, 1,2-diamino-reactions with dicarbonyl compounds aza macrocycles from, 902 Benzene, 4 methylthionitroso-metal complexes, 804 Benzenedithiolates metal complexes, 605... 

Reduction of the porphyrin 7t-system results in a bathochromic shift and an enhancement of the extinction coefficient of the Q-band. There are characteristic differences between bacteriochlorins and isobacteriochlorins. An ultraviolet spectrum of a pyrrocorphin (15) has been described, proving earlier reports on a synthesis of this compound to be erroneous (85CC1604). 

During the last decade a remarkable number of hydroporphyrins have been synthesized, mostly with regard to biochemical problems. Ring synthesis proves particularly important in this area since a possible control of single steps of the synthetic sequence allows for an establishment of a specific substitution pattern. Examples of this section are presented in a file of decreasing size of the re-systems, i.e., chlorins are followed by bacteriochlorins, etc. 

Synthesis and characterization of other related macrocycles, including chlorins, " isobacteriochlorins, bacteriochlorins, mono- and dioxoporphyrins, " other more highly saturated hydroporphyrins, N-alkyl- or A-arylporphyrins, some of which are chiral, porphodimethenes, thiaporphyrins, " oxaporphyrins, N-confused " and carbapor-phyrins, porphycenes " and corrphycenes, " tetraazaporphyrins, phthalocyanines, the ring-expanded sapphyrins, texaphyrins and others, and the ring-contracted corroles " and corrolazines have also been synthesized and are discussed in the indicated references. 

The Synthesis of Chlorins, Bacteriochlorins, Isobacteriochlorins and Higher Reduced Porphyrins... 

Cavaleiro et al. developed methodologies based on cycloaddition transformations of porphyrins leading to the synthesis of compounds like chlorins and bacteriochlorins which have strong absorptions in the visible region near or above 650 nm. The reactive diene and dipolarophile species have been o-quinodimethanes [159], azomethine ylides [160] and nitrones [161]. The 1,3-dipolar cycloaddition approach led to the synthesis of glycoderivatives of the chlorin and bacteriochlorin types (Scheme 45) [162]. 

Because of its long-wavelength absorption close to 800 nm, naturally occurring bacteriochlorophylls are ideal candidates for PDT. However, due to their unstable nature, synthesis of stable bacteriochlorins has been a challenge for porphyrin chemists worldwide. 

Most of the naturally occurring bacteriochlorins (e.g., 132) have absorptions between 760 and 780 nm and are extremely sensitive to oxidation, resulting in a rapid transformation into the chlorin state 133 which generally has an absorption maximum at or below 660 nm (Scheme 37). Furthermore, if a laser is used to excite the bacteriochlorin in vivo, oxidation may result in the formation of a new chromophore absorbing outside the laser window, reducing its photodynamic efficacy. Due to the desirable photophysical properties of bacteriochlorins, there has been increasing interest in the synthesis of stable bacteriochlorins from bacteriochlorophyll a or other similar tetrapyrrolic systems. 

Pandey et al. and Dolphin and coworkers223 reported the synthesis of new bacteriochlorins which involved the double... 

Scheme 43. Synthesis of bacteriochlorins by the double Diels-Alder approach.

Mironov, A. F. Grin, M. A. Synthesis of chlorin and bacteriochlorin conjugates for photodynamic and boron neutron capture therapy. J. Porphyrins Phthalocyanines 2008,12,1163—1172. 

Grin, M. A., Semioshkin, A. A., Titeev, R. A. et al. 2007. Synthesis of a cycloimide bacteriochlorin p conjugate with the cZoso-dodecaborate anion. Mendeleev Commun. 17 14—15. 

Almost 30 years ago, Whitlock et al. ° developed an efficient diimide reduction method for the synthesis of bacteriochlorins and isobacteriochlorins from porphyrins. Diimide reduction of metal-free tetraphenyl chlorin afforded tetraphenyl bacteriochlorin, while reduction of the corresponding zinc analog produced... 

Morgan et al. showed that bacteriochlorin-like macrocycles can also be generated by cyclization of either 5,10- or 5,15-bis[(ethoxycarbonyl)vinyl]-porphyrins. However, the resulting products rapidly decomposed upon exposure to air, thus precluding their use as photosensitizers for PDT. For developing a general synthesis of stable bacteriochlorins, the same authors followed the pinacol-pinacolone approach in preparing ketochlorins 22 and 23. In brief, dehydration of 19 produced a mixture of 20 and... 

---