Antibiotics relative configuration

Characterisation of the antibiotic monordene (also referred to as radicicol) with the elemental composition Cig/Zz/OgCl isolated from Monosporium bonorden gave the macrolide structure 1. The relative configuration of the H atoms on the two conjugated double bonds (6,7-cis, %,9-trans-) could be deduced from the 60 MHz H NMR spectrum The relative configuration of the C atoms 2-5, which encompass the oxirane ring as a partial structure, has yet to be established. 

Determination of the absolute configuration of 27 (a constituent of certain peptide antibiotics, the relative configuration for all racemic stereoisomers 27 - 30 was determined as summarized on p 472 and 485) by a correlation-type synthesis commencing from (S)-vinylglycine (26, R = H)203. Note that this synthesis serves only to determine the absolute configuration at C-2 of 27 (and of 29). 

Another example is part of the structural elucidation of 3-hydroxy-5-methyl-2-piperidinecar-boxylic acid, which has been identified as a component of some peptide antibiotics (see p 440). The relative configuration was determined by preparing (unselectively) all four racemic diastereomers 8-11 and subsequent H-NMR and equilibration studies. Thus, 8 and 9 were each converted to an equilibrium mixture of these two isomers in the ratio 2 1 (see p 472). From this experiment it was concluded, that 8 and 9 are epimeric at C-2, and that the more stable isomer has the 2,3-trans configuration 8 (the latter conclusion was based on previous results). In the same way the relative configuration at C-2 and C-3 of 10 and 11 was established274. 

Recently, workers at Abbott Laboratories reported the isolation and prelintinary characterization of a new nargenicin-type Z u-macrolide antibiotic, coloradocin, 8, from cultures of Actinoplanes coloradoensis. H The novel bislactonic structure proposed for 8 was based on a detailed spectroscopic examination which included extensive homo- and heteronuclear 2D NMR studies. 12 Although these investigations failed to unequivocally define the relative configuration of the macrocyclic chirality, the key structural elements of 8, including an oxa-bridged octalin... 

The xanthoquinodins A1-A3 and B1-B2 (1058 to 1062, Fig. 13.28) were identified initially as anticoccidal antibiotics isolated from a Humicola sp. Feeding experiments with and extensive spectroscopic data analysis on the resulting isotopically enriched compounds allowed for the structure determination of these five compounds (678,679). These heterodimers, like the beticolins, also result from the coupling of a xanthone with an anthraquinone, although the coupling is now in an end-to-tail fashion. The relative configuration at C-W and C-14 is S and R, respectively, and C-2 is S and C-3 is S. 

The following stereospecific synthesis is part of the scheme used by E. J. Corey of Harvard University in the s)mthesis of erythronolide B, the precursor of the erythromycin antibiotics. In this remarkably simple set of reactions, the relative configurations of five chiral centers are established. 

The novel quinolone antibiotics, quinolactacins A-C (Schemes 15 and 16 Tables X and XI), were first discovered from the cultured broth of Penicillium sp. EPF-6, which was isolated from the larvae of the mulberry pyralid (Margaronia pyloalis Welker) (197,198). More recently, the two quinolactacin A diastereo-mers were isolated from a solid-state fermentation of P. citrinum 90648 and named quinolactacin A1 and quinolactacin A2. The relative configuration of... 

Madindoline A (7) and B (ent-8) are potent inhibitors of interleukin 6. In a total synthesis [21] that also intended to determine the relative and absolute configurations of these novel antibiotics, the densely functionalized cyclopen-tene-l,3-dione ring of 7 and 8 was elaborated via RCM of diene-diol 2 (Scheme 1). 

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