Spiro-ortholactone

The orthosomycin antibiotics [46] are stmcturally characterized by one or more interglycosidic spiro-ortholactone linkages, replacing the traditional acetal junctions [47]. The natural occurrence of orthoesters is rare, but within recent years several examples of antibiotics possessing this common stmctural feature have been described. The orthosomycins include flambamycin, the eveminomicins-B, -C, -D and -2, hygromycin, the destomycins-A, -B and -C and the antibiotics SS-56-C and A-396-I (O Fig. 7). The orthosomycins have been divided into two... 

An intramolecular Lewis-acid catalyzed addition of an enol silyl ether to the spiro-ortholactonic center of 8 took full advantage of the stereoelectronic... 

Tetramers containing deoxy-sugars to have been synthesised are O-a-D-Galp-(l->3)-0-a-D-Glg7-(l- 3)-0-a-L-Rh -(l- 4)-D-ribitol, an 5. Pneumoniae polysaccharide unit, and a tetrasaccharide component of the orthosomycins (Chapter 19) containing a spiro-ortholactone feature. 

Spiroethers 241 and spiroketals 242 can be easily prepared by condensation of readily available annelating agents such as 106a with cyclic ketones, for example 243 and ortholactones 244, respectively. Both spiro-derivatives 241 and 242 are obtained in excellent yields (Scheme 13.88). 

Kocienski and his co-workers have described the novel intramolecular Lewis acid catalysed directed aldol reaction of the spiro-cyclic ortholactone (18 ) prepared from the fragments (185) and (186), to set up the spiro-acetal portion (I88). Milbemycin (189) was then secured from (I88) by sequential sulphone-based (Julia) olefination reactions to produce the double bonds at C10-... 

The ortholactone 14 could be prepared from the 0-benzylated 2-deoxylacmne by sequential treatment with triethyloxonium tetrafluoroborate and sodium ethoxide. Subsequent orthoester exchange could be effected with 1,2-diols to give spiroortholactones such as 15. When the glucosyl thiohydroximate 16, or its a-aiKHno, was photolysed in the presence of NBS, the spiro-oxathiazole 17 was obtained in 50% yield. 

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