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A route under development for the synthesis of bacteriochlorophyll a and analogues relies on joining an AD-dihydrodipyrrin (bearing a D-ring carboxaldehyde) and a BC-dihydrodipyrrin (bearing a C-ring β-ketoester group and a B-ring dimethoxymethyl group) via Knoevenagel condensation followed by double-ring closure (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol). Prior synthetic studies afforded the bacteriochlorophyll skeleton containing a gem-dimethyl group in ring B, a trans -dialkyl group in ring D, and a carboethoxy group at the 3-position of ring A. To explore the incorporation of native substituents, the synthesis of two bacteriochlorophyll analogues thereof was pursued, one with 12-methyl and 3-carboethoxy groups and the other with 2,12-dimethyl and 3-acetyl groups. The 12-methyl group resulted in half the yield ( versus the unsubstituted analogue) in the Knoevenagel reaction, but insignificant effects in all other steps including the rate and yield of double-ring closure despite the known effects of alkyl groups to facilitate electrophilic substitution of pyrroles. The 2-methyl-3-acetyl group, however, resulted in diminished yields in several steps, including the Knoevenagel reaction, but not the double-ring closure. The results point to obstacles and openings on the path to total syntheses of the native pigments. 

Tolyporphins A–R constitute fundamentally distinct members of the tetrapyrrole pigments of life family. The 18 members present diversity at multiple levels including the chromophore (dioxobacteriochlorin, oxochlorin, porphyrin); composition of the pyrroline substituents (hydroxy, acetoxy, or one of four C -glycosides); and stereochemical configuration of the pyrroline substituents. Eleven of the 18 tolyporphins contain at least one C -glycoside; each C -glycoside has a β, d configuration and lacks a 6′-hydroxy group: 3′,6′-dideoxygalactose (common name abequose), 2′- O -acetyl-3′,6′-dideoxygalactose (2′- O -acetylabequose), 6′-deoxygalactose ( d -fucose), or 6′-deoxygulose (antiarose). Rare are such glycosides outside of tolyporphins: (2′- O -acetyl)abequose is reported only in the glycan polymer attached to the cell wall of two strains of Gram-negative bacteria, and antiarose is reported in one bacterial natural product and ∼50 plant cardiac glycosides. Eight of the 18 tolyporphins are bis( C -glycosides), an exceptionally uncommon motif in natural products. The biosynthetic pathways to the family of tolyporphins remain unknown. Regardless of such diversity, each tolyporphin member shares a common pattern of perimeter methyl substituents that coheres with derivation from uroporphyrinogen III, the universal precursor in the established pathway to native tetrapyrroles. Here, transformations required to convert uroporphyrinogen III to all 18 tolyporphins are considered in the context of plausible biosynthetic pathways. Heme d 1 , perhaps the closest relative (yet still a distant cousin) of tolyporphins, and for which key biosynthetic transformations remain undeciphered, provides a point of reference. Taken together, the work provides the foundation for bioinformatic searching for enzymes associated with the biosynthesis and diversification of tolyporphins. 

Native chlorophylls and bacteriochlorophylls share a common trans-substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substituents and tailorable A-ring substituents have been synthesized. The synthesis relies on a Schreiber-modified Nicholas reaction to construct the stereochemically defined precursor to ring D, a dialkyl-substituted pent-4-ynoic acid. The carboxylic acid group of the intact propionic acid proved unworkable, whereupon protected propionate (−CO2tBu) and several latent propyl ethers were examined. The tert-butyldiphenylsilyl-protected propanol substituent proved satisfactory for reaction of the chiral N-acylated oxazolidinone, affording (2S,3S)-2-(3-((tert-butyldiphenylsilyl)-oxy)propyl)-3-methylpent-4-ynoic acid in ∼30% yield over 8 steps. Two variants for ring A, 2-tert-butoxycarbonyl-3-Br/H-5-iodo-4- methylpyrrole, were prepared via the Barton−Zard route. Dihydrodipyrrin formation from the pyrrole and pentynoic acid entailed Jacobi Pd-mediated lactone formation, Petasis methenylation, and Paal−Knorr-type pyrroline formation. The two AD- dihydrodipyrrins bear the D-ring methyl and protected propanol groups with a stereochemical configuration identical to that of native (bacterio)chlorophylls, and a bromine or no substitution in ring A corresponding to the 3-position of (bacterio)chlorophylls. The analogous β-position of a lactone−pyrrole intermediate on the path to the dihydrodipyrrin also was successfully brominated, opening opportunities for late-stage diversification in the synthesis of (bacterio)chlorophylls. 

A long-term goal is to gain synthetic access to native photosynthetic bacteriochlorophylls. A recently developed route entails Knoevenagel condensation of an AD dihydrodipyrrin ( I , bearing a carboxaldehyde attached to pyrroline ring D) and a BC dihydrodipyrrin ( II , bearing a β-ketoester attached to pyrrole ring C) to form the Z / E -enone. Acid-mediated double-ring closure of the E -enone III-E (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol) affords the bacteriochlorophyll skeleton BC-1 containing the isocyclic ring (ring E), a trans -dialkyl group in ring D, and a gem-dimethyl group in ring B. Prior work established the synthesis and the integrity of the resulting trans -dialkyl groups and bacteriochlorin chromophore. The counterpart report here concerns an in-depth study of conditions for the double-ring closure: catalyst/solvent surveys; grid search including time courses of [ III-E ] versus [acid] concentrations emphasizing equimolar, inverse molar, and variable acid lines of inquiry; and chlorin byproduct quantitation. Key findings are that (1) the double-ring closure can be carried out in 4 h ( t 1/2 ∼ 40 min) instead of 20 h, affording ∼1/5th the chlorin byproduct (0.16%) while maintaining the yield of BC-1 (up to 77%); (2) the separate Z / E -enones of III have comparable reactivity; (3) sub-stoichiometric quantities of acid are ineffective; (4) the Knoevenagel condensation (40 mM, room temperature, piperidine/acetic acid in acetonitrile) and the acid-mediated double-ring closure (0.20 mM, 80 °C, Yb(OTf) 3 in acetonitrile) can be carried out in a two-step process; and (5) zinc insertion to form ZnBC-1 is straightforward. Together, the results enable streamlined conversion of dihydrodipyrrin reactants to the bacteriochlorophyll model compounds. 

Riley oxidation of advanced heterocyclic intermediates (dihydrodipyrrins and tetrahydrodipyrrins) is pivotal in routes to synthetic hydroporphyrins including chlorins, bacteriochlorins, and model (bacterio)chlorophylls. Such macrocycles find wide use in studies ranging from energy sciences to photomedicine. The key transformation (–CH3 → –CHO) is often inefficient, however, thereby crimping the synthesis of hydroporphyrins. The first part of the review summarizes 12 representative conditions for Riley oxidation across diverse (non-hydrodipyrrin) substrates. An interlude summarizes the proposed mechanisms and provides context concerning the nature of various selenium species other than SeO2. The second part of the review comprehensively reports the conditions and results upon Riley oxidation of 45 1-methyltetrahydrodipyrrins and 1-methyldihydrodipyrrins. A comparison of the results provides insights into the tolerable structural features for Riley oxidation of hydrodipyrrins. In general, Riley oxidation of dihydrodipyrrins has a broad scope toward substituents, but proceeds in only modest yield. Too few tetrahydrodipyrrins have been examined to draw conclusions concerning scope. New reaction conditions or approaches will be required to achieve high yields for this critical transformation in the synthesis of hydroporphyrins. 

Photosynthesis can be challenging for instructors to teach and uninteresting for students to learn, but this shouldn't be the case. An activity developed by middle-school educators and university scientists lets students see how red light emitted from sunlit plants is captured by satellites to measure global photosynthesis. In plants, most of the absorbed light energy is channeled into photosynthesis, and the tiny amount that is emitted as red fluorescence is not visible by naked eye but is detectable by satellites. When chlorophyll is removed from plants into a solution – uncoupled from the photosynthetic apparatus – chlorophyll still is green and absorbs light, but the absorbed light energy has nowhere to go, and a large red glow is visible. In a readily accessible 1-hour middle-school classroom activity, students extract chlorophyll from spinach using rubbing alcohol (91% isopropyl alcohol) and then observe the abundant red fluorescence upon illumination with a flashlight. This simple observation of the red glow (fluorescence) from chlorophyll provides a terrific anchor for teaching photosynthesis in a biological, agricultural and global ecology context, thereby inspiring students to better appreciate the fascinating world of plants.