Branched-chain antibiotic components

Diisobutylaluminum hydride was also employed (153) for the reduction of 2,6-dideoxy-3-C-methyl-D-arabmo-hexono-1,4-lactone (121) to an antibiotic component, the branched-chain sugar evermicose (2,6-dideoxy-3-C-methyl-D-nrabmo-hexose, 122). The L-enantiomer of 122 (olivomycose, 125a), L-amicetose 125b, and 2,6-dideoxy-3-C-methyl-L-n Zw-hexose (l-... 

The naturally occurring, branched-chain sugars were classified as rare sugars1,2 until the 1960 s, but the discovery of numerous new sugars as the glycosidic component of antibiotics during the past two decades has stimulated extensive research on their chemistry and biochemistry,... 

D-Apiose can be isolated from parsley and is a component of the cell wall polysaccharide of various marine plants. Among its novel structural features is the presence of only a single chirality center. L-Vancosamine is but one portion of vancomycin, a powerful antibiotic that has emerged as one of only a few antibiotics that are effective against drug-resistant bacteria. L-Vancosamine is not only a branched-chain carbohydrate, it is a deoxy sugar and an amino sugar as well. 

Branched-chain monosaccharides have now been detected as components of bacterial polysaccharides. The known examples include yersiniose [3,6-dideoxy-4-C-(hydroxyethyl)-D-xy/o-hexose228] from Y. pseudotuberculosis, a 3-C-(hydroxymethyl)pentofuranose from Coxiella bumetti,229 and 6-deoxy-3-C-methylhexoses from the same organism and from Nitrobacter hamburgiensis.229 Several branched-chain monosaccharides were identified as components of antibiotics, and the pathways of their biosynthesis in bacteria were studied. These investigations were discussed in detail by Grisebach in this Series.230 The usual precursors for the formation of the monosaccharides of this group are the nucleoside 6-deoxyhexosyl-4-ulose diphosphates 7a and 7b. 

Several compounds of this type, formally derived from aldoses by oxidation of the terminal CH2OH group to -CHO, have been prepared. Dialdoses arise as intermediates in structural studies, but they are also valuable starting materials for synthetic conversions, in particular for natural-product synthesis. A branched-chain dialdose, streptose (167), occurs as a component of the antibiotic streptomycin. The structure of streptose was elucidated after extensive investigations of its derivatives and transformation products.371 The 2,5-dimethoxytetrahydrofuran fulvanol (168), an analogue of apiose, has been isolated from the plant Hemerocallis fulva 12... 

More than a dozen branched-chain, deoxy sugars have now been discovered as components of antibiotics. One review on their biosynthesis4 and two5,6 on the chemistry and biochemistry of branched-chain sugars have appeared. These sugars can be divided into two groups according to their biosynthesis. 

During the past nine years the subject of total synthesis of sugars and cyclitols has been vividly developed. The discovery of a large number of unusual sugars in nature—deoxy, amino, branched chain sugars (many of them components of antibiotics)—made their synthesis attractive. On the other hand, improvements in organic reagents and synthetic methods allowed a return to older preparations which could be now better performed. Finally, some synthetic ideas already described in this series, in the first chapter of the volume on the total synthesis of carbohydrates, are further expanded. 

A new cytotoxic antibiotic cytorhodin X from a Streptomyces strain has been shown to be an unusual anthracyclinone 9a-glycoside 6. Another new anthracycline antibiotic, dutomycin, also obtained from a Streptomyces strain, contains a disaccharide component 7 including the branched chain sugar L-axenose. ... 

The structure of the branched-chain amino-disaccharide (106), a component of a novel glycopeptide antibiotic of the vancomycin group, has been elucidated by FAB mass spectrometry and 2D n.m.r. spectroscopy. ... 

The 4-epj-mycosamine unit (1) and the branched-chain 4-epi-vancosamine unit (2) (of assumed L-configuration) have been found as glycosidic components of antibiotics. 

New paulomycin variants (35) have been isolated from S. paulus as minor components of the antibiotic complex they contain the same nucleus and sugars as do the major components A and B, but with differing acids esterifying the branched-chain sugar this sugar is... 

Pillarose, a branched-chain component of the antibiotic pillaromycin A, has been shown by jy-ray crystallography i and synthesis to be a 2,3,6-trideoxy-4-C-glycolylhexose (246) and not a 2,3,6-trideoxy-2-C-glycolyIhexos-4-uIose as originally proposed (see Chapter 15). 

The branched-chain amino-sugar (1) has been identified as a component sugar in glycopeptide antibiotics (see also Chapter 19). ... 

Paulsen s group has reported the synthesis of derivatives (256) and (257) of the hydroxyethyl-branched octose that is found as a component of the quinocycline complexes isolated from Streptomyces aureofaciens. The route from the epoxyketone (255) is outlined in Scheme 59. An identical route was used to prepare branched-chain analogues in the o-series, in which it was shown that acid-catalysed methanolysis of the hydroxyethyl-branched derivative (258) yielded the more stable isomer (259) via the anhydro-sugar d-(257). Paulsen s group has also described a synthesis of a derivative (260) of pillarose (see Vol. 9, p. 99), a component of the antibiotic pillaromycin, using the dianion (261) prepared from 2-hydroxymethyl-l,3-dithiane to introduce the branch at C-4 (Scheme 60). A similar approach, using the anion derived from 2-methyl-l,3-dithiane, and subsequent desulphurization and reduction, etc., was adopted in a synthesis of a derivative (262) of aldgarose (4,6-dideoxy-3-C-[(i )-l-hydroxyethyl]-D-W6o-hexopyranose 3,3 -cyclic carbonate) (cf. Vol. 8, p. 100). 

An ansamycin antibiotic produced by Streptomyces spectabilis with antibacterial (against tuberculosis pathogens), antiviral, and antitumor activities. S. occurs as a multi-component mixture of up to ten individual compounds (S. A to G, J, K, and U) with S. C (methyl streptovaricate, C4oH5,NO,4, Mr 769.84, amorphous, mp. 189-191 °C, [a][) 4-602°) as the main component. The S. are inhibitors of bacterial RNA-polyme-rase as well as the reverse transcriptase of oncogenic viruses. The biosynthesis of the aromatic core branches off from the shikimic acid pathway while the alkyl chain is formed on the polyketide pathway. 

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