Prodigiosin

Prodigiosin (12). The first reported biosynthetic application of Fourier-trans-form (FT) C n.m.r. techniques was to the study of prodigiosin (12). Earlier 

Labelled prodigiosins were prepared by feeding 1- C- and 2- C-enriched sodium acetate (63%) to the bacterium Serratia marcescens. The enhanced sensitivity available by the FT mode of operation is underscored in this study since the n.m.r. spectra were recorded on 360 mg ml of natural-abundance prodigiosin in 18 minutes, on 180 mgml of the material from CHj COjNa labelling in 20 minutes, and on 17.9mgml of CHaCOjNa-labelled pigment in 6.7 hours. 

Figwe 6 Proton-noise-decoupled n.m.r. spectrum of prodigiosin hydrochloride (Reproduced by permission of R. J. Cashley). 

The assignment of the seven quaternary carbon signals was aided by comparison with the shift values of model compounds (13), (14), and (15). Further confirmation of the quaternary a2 and b2 shift positions was secured with an A3,A534,c4-tetradeuterio-derivative, in which the b2 carbon remained coupled to the 1 portion in the deuteri ted material. Progressive saturation experiments also confirmed the presence of six quaternary carbons, at a2, b2, b3, c2, c3, and c5. 

The methylene carbon resonances were assigned by strong CW irradiation in the methylene n.m.r. absorption region of the n-amyl side-chain. This resulted in residual coupling (J values consistent with the n.m.r. shifts of the 

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Natural Products. The prodigiosins are antibacterial and antiftmgal orange-red pigments based on the basic pyrryl—dipyrrylmethene unit [22187-69-5] (31). 

For an excellent review on the chemistry and biology of273 and the related prodigiosin alkaloids, see Fiirstner A (2003) Angew Chem Int Ed 42 3582... 

A key step in Boger s synthesis of prodigiosine and related compounds is the oxidative cyclization of dipyrrolyl ketones such as 35 to give 36 in excellent yield [35, 36]. Noteworthy is the use of polymer-supported Pd(OAc)2 in this chemistry. 

Prodigiosin (Streptorubin B) (192) Tri-pyrrole antibiotic Obatoclax (GX15-070)(193) Oncology Bcl-2 inhibition Phase I/n Gemin X 911,912... 

The first efficient application of a well-defined ruthenium indenylidene complex in metathesis was described in 1999 by Frirstner for the total synthesis of a cyclic prodigiosin derivative, a potential lead compound for the development of immunosuppressive agents. The RCM using the ruthenium indenylidene complex DC (10 mol%) as precatalyst leads to the transformation of the N-protonated diene into the desired macrocycle in 65% yield (Equation 8.8) [43]. 

Table 5.47. 13C Chemical Shifts (<5C in ppm) of Prodigiosin Hydrochloride (Solvent CHClj) [1015].

While interesting neutral alternatives to the unsaturated expanded porphyrin derivatives, calix[n] pyrroles (n = 4, 5, 6, 8) are relatively limited in their scope for anion binding because of the constraints of the cavity size. Nevertheless pyrroles linked by an sp3 hybridised carbon atom are of considerable interest because of their resemblance to the anti-cancer agents the prodigiosins (Section 4.2.4), moreover pyrrole anion-receptor chemistry is synthetically versatile and hence a range of acyclic pyrroles and hybrid amidopyrroles such as 4.50-4.52 have been developed, particularly by the groups of... 

Biological anion binding proteins and naturally occurring receptors such as the prodigiosins provide much of the inspiration for anion receptor chemistry. 

From the Japanese bryozoan Bugula dentata, an antimicrobial blue pigment (121) was isolated (111) and found to be identical with a tetrapyr-role previously isolated from a mutant strain of Serratia marcescens (112). The color of the bryozoan B. dentata is unusually dark blue, suggesting that the pigment 121 is ubiquitously present in the animal. Whether compound 121 is biosynthesized by the bryozoan itself or by an associated microorganism or derived from food sources such as prodigiosin-producing bacteria is still unknown. 

Anions can also be transported across membranes. In Nature, Cl- is transported by prodigiosins which comprise three conjugated pyrrole groups and a lipophilic alkyl... 

Artificial analogues of the chloride transporter prodigiosin are effective symport HC1 carriers as exemplified in the model systems developed by the groups of Gale [39] and Davis [40], Biological inspiration is also behind another Cl- carrier. Cholic acid is a naturally occurring bile acid that functions as a surfactant in the intestine. Derivatives with three binding sites known as cholapods are able to transport isolated anions across lipid bilayers [41],... 

Sato T et al (1998) Prodigiosins as a new group of II+/CI symporters that uncouple proton translocators. J Biol Chem 273 21455-21462... 

Gale PA et al (2005) Co-transport of H+/CE by a synthetic prodigiosin mimic. Chem Commun 3773-3775... 

Seganish JL, Davis JT, Prodigiosin is a chloride carrier that can function as an anion exchanger. Chem Commun 5781-5783... 

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