skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Study of conditions for streamlined assembly of a model bacteriochlorophyll from two dihydrodipyrrin halves
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.  more » « less
Award ID(s):
1760839
PAR ID:
10285887
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
New Journal of Chemistry
Volume:
45
Issue:
2
ISSN:
1144-0546
Page Range / eLocation ID:
569 to 581
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; (, New Journal of Chemistry)
    null (Ed.)
    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. 
    more » « less
  2. ; (, Helvetica Chimica Acta)
    Abstract We describe convenient preparations ofN,N′‐dialkyl‐1,3‐propanedialdiminium chlorides,N,N′‐dialkyl‐1,3‐propanedialdimines, and lithiumN,N′‐dialkyl‐1,3‐propanedialdiminates in which the alkyl groups are methyl, ethyl, isopropyl, ortert‐butyl. For the dialdiminium salts, the N2C3backbone is always in thetrans‐s‐transconfiguration. Three isomers are present in solution except for thetert‐butyl compound, for which only two isomers are present; increasing the steric bulk of theN‐alkyl substituents shifts the equilibrium away from the (Z,Z) isomer in favor of the (E,Z), and (E,E) isomers. For the neutral dialdimines, crystal structures show that the methyl and isopropyl compounds adopt the (E,Z) form, whereas thetert‐butyl compound is in the (E,E) form. In aprotic solvents all four dialdimines (as well as the lithium dialdiminate salts) adoptcis‐s‐cisconformations in which there presumably is either an intramolecular hydrogen bond (or a lithium cation) between the two nitrogen atoms. 
    more » « less
  3. ; (, The Journal of Organic Chemistry)
    null (Ed.)
    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. 
    more » « less
  4. ; ; ; ; (, Synthesis)
    Haak, Susanne (Ed.)
    Abstract A new octaphenyl[4.4]triphenylparacyclophanediene was readily synthesized in six steps from p-xylene via the installment of bromine atoms, replacement with a vinyl group, carbonylative coupling, intermolecular followed by intramolecular double Grubbs olefin metathesis, Knoevenagel condensation, and Diels–Alder cycloaddition. The belt-shaped structure and trans-stereochemistry of the alkene moieties of the octaphenyl[4.4]triphenylparacyclophane and a synthetic intermediate, 2,21-dioxo-11,30-diene[3.4.3.4]paracyclophane, were determined by X-ray crystallography. The synthetic methodology leading to octaphenyl[4.4]triphenylparacyclophane is applicable for the synthesis of substituted triphenylparacyclophanes and possibly their corresponding bis-hexabenzocoronenylparacyclophanes via a Scholl–Mullen oxidative aryl-aryl coupling reaction. 
    more » « less
  5. ; (, Journal of Chemical Technology & Biotechnology)
    Abstract BACKGROUNDKnoevenagel condensation is an important tool for building carbon–carbon (CC) bonds, especially when catalyzed by enzymes to enable a potentially high chemo‐, regio‐ and/or stereoselectivity. Although many Knoevenagel condensation reactions are carried out in aqueous solutions, insoluble hydrophobic substrates often lead to poor catalytic efficiencies. The use of water‐miscible organic solvents improves the substrate solubilization, but usually induces activity suppression or inactivation of enzymes. There is a great need to develop alternative solvents for both substrate dissolution and enzyme compatibility in CC bond formation reactions. RESULTSOur group previously developed dual‐functionalized water‐mimicking ionic liquids (ILs) for the activation and stabilization of hydrolases (e.g. lipase and protease). In the present study, we evaluated the Knoevenagel condensation of 4‐chlorobenzaldehyde with acetylacetone, and found that porcine pancreas lipase in water‐mimicking ILs carrying ammonium, imidazolium and benzimidazolium cations enabled higher reaction rates (up to 3.22 μmol min−1 g−1lipase) and better yields thantert‐butanol, glymes and [BMIM][Tf2N]. Interestingly, tertiary amide solvents such asN‐methyl‐2‐pyrrolidone (NMP),N,N‐dimethylformamide (DMF) andN,N‐dimethylacetamide (DMAc) led to 8.2‐ to 11.1‐fold increases in the initial rate (up to 35.66 μmol min−1 g−1lipase) when compared with dual‐functionalized ILs, which is likely due to some synergistic effect of these tertiary amides with the lipase. CONCLUSIONDual‐functionalized ILs based on ammonium, imidazolium and benzimidazolium cations improved Knoevenagel condensation reaction rates and yields when compared withtert‐butanol and glymes. Tertiary amides (NMP, DMF and DMAc) significantly increased the reaction rate. © 2024 The Authors.Journal of Chemical Technology and Biotechnologypublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI). 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email