Pironetin isolation

Discovery Pironetin (1) was isolated as a plant growth regulator that induces shortening of the plant height of rice [1,2] and as an immunosuppressor that inhibites the blastogenesis of both T and B cells [3]. 

Kobayashi, S., Tsuchiya, K., Harada, T., et al. (1994). Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958 I. Taxonomy, production, isolation and preliminary characterization. J. Antibiot., 47, 697-702. 

ABSTRACT Discodermolide and pironetin are two immunosuppressive agents with antitumor activity. The isolation, structure elucidation, biological activity are reported as well as the synthetic routes to these two compounds. Five syntheses of discodermolide and seven syntheses of pironetin are described. 

Pironetin was originally isolated from the culture broth of Streptomyces sp as a plant growth regulator which induced shortening of the plant height of rice [73, 74]. In 1996, it was also reported that PA-48153 C, which was identical to pironetin and showed potent immunosuppressive... 

The structure of pironetin was determined to be (5/ ,6/ )-5-ethyl-5,6-dihydro-6[(jE )-(2/ ,35,4/ ,55)-2-hydroxy-4-methoxy-3,5-dimethyl-7-nonenyl]-2H-pyran-2-one by FAB-MS, H and 13C NMR, COSY, COLOC, DEPT, IR, X-ray crystallographic analyses and adapted Mosher s method to determined the absolute configuration [74]. The biosynthesis of pironetin appeared to involve assembly of acetate, propionate and butyrate precursors. Four fermentation experiments were carried out in order to determine the biosynthetic origin of the carbon skeleton and oxygen atoms of pironetin. [1-13C] Acetate, [2-13C]acetate, [1,2-13C] acetate, [l-13C]propionate, [l-1 C]butyrate and L-[methyl-I3C]methionine were led separately to Streptomyces sp. culture and pironetin was isolated and purified. Analysis of pironetin by 13C NMR showed that pironetin was derived from four acetate units, two propionate units, one butyrate unit and one methyl unit of methionine [78] (Fig. 4). 

Compound (80), a structural isomer of umuravarumbolide (55), is a minor constituent of Cryptocarya latifolia 89). The immunosuppressive agent, (—)-PA-48153 (81), has been isolated from Streptomyces prunicolor sp. PA 48153 (90). The same compound, obtained from Streptomyces sp. NK10958 and shown to be a plant growth regulator, has been named pironetin, and the structure based on spectral data, confirmed by X-ray analysis 91, 92) and synthesis 93). 

Kobayashi, S., K. Tsuchiya, T. Harada, M. Nishide, T. Kurokawa, T. Nakagawa, N. Shimada, and K. Kobayashi Pironetin, a Novel Plant Growth Regulator Produced hy Streptomyces sp. NK 10958. 1. Taxonomy, Production, Isolation and Preliminary Characterization. J. Antibiot., 47, 697 (1994). 

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