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Issue 4, 2012
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A tandem combinatorial model for the prebiogenesis of diverse tetrapyrrole macrocycles

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The extant biosynthesis of tetrapyrrole macrocycles has been considered a paradigm for the prebiotic formation of such molecules, yet only a few analogous non-enzymic reactions along the overall process have been demonstrated. In a prior study, the aqueous non-enzymic reaction of a dione and an aminoketone (δ-aminolevulinic acid) afforded uroporphyrinogen, Nature's last universal precursor to all extant tetrapyrroles. Here, in one flask the non-enzymic combinatorial reaction of two diones (substituents = acetic acid and methyl) and two aminoketones (substituents = propionic acid and ethyl) yields four pyrroles, which upon subsequent combinatorial reaction afford a distribution of porphyrinogens. A software program for virtual library generation predicts 538 porphyrinogens from this [2 × 2] reaction (owing to combinations and permutations) of which there are 25 sets of isomers based on condensed formulas of substituents. The collection spans the entire range of polarity enabled by the biosynthesis including uro- (number of carboxylic acids = 8), copro- (4), meso- (2), and etio-porphyrinogen (0). The first two are successive intermediates in the extant biosynthesis, the latter two resemble in polarity the advanced biosynthetic products protoporphyrin and chlorophyll. Upon consideration of substituent patterns, the porphyrins (obtained by oxidation of the porphyrinogens) can be grouped into one of four polarity categories (predicted percentage): hydrophilic (0.4%), uncertain (83.6%), amphiphilic (15.6%), and hydrophobic (0.4%). HPLC and mass spectrometry data are consistent with expectations to the limit of analytical capabilities. Thus, in terms of the polarity of the tetrapyrrole macrocycles formed, an all-at-once non-enzymic combinatorial process recapitulates features of the stepwise biosynthetic pathway.

Graphical abstract: A tandem combinatorial model for the prebiogenesis of diverse tetrapyrrole macrocycles

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The article was received on 19 Dec 2011, accepted on 25 Jan 2012 and first published on 16 Feb 2012

Article type: Paper
DOI: 10.1039/C2NJ21050A
Citation: New J. Chem., 2012,36, 1057-1069

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    A tandem combinatorial model for the prebiogenesis of diverse tetrapyrrole macrocycles

    M. Taniguchi, A. R. M. Soares, V. Chandrashaker and J. S. Lindsey, New J. Chem., 2012, 36, 1057
    DOI: 10.1039/C2NJ21050A

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