Antibiotics orthosomycins

Addition of diols to the carbonyl lactone group leads to the formation of cyclic orthoesters. Compounds containing a spiro, cyclic orthoester inter-linkage at the anomeric carbon atom are of interest, as this type of structure is found in the oligosaccharide antibiotics orthosomycins (91) (such as ever-ninomicin, flambamycin, and avilamycin). 

The small number of novel chlorophenol-oligosaccharide antibiotics (orthosomycins) presented in the earlier survey (7 ) has been expanded to include a few new examples. However, the highlight in this area is the total synthesis of eveminomicin 13,384-1 (ziracin Sch 27899) (2224) (2020-2022), which is found in cultures of Micromonospora carbonacea var. africana (2023-2025). This organism has also furnished the related eveminomicins 2225, 2226,13,384-5 (Sch 27900) (2227), Sch 49088 (2228) (2023-2026), and Sch 58761 (2229) (2027). 

Avilamycin is a polyether antibiotic of the orthosomycin family that consists of a six-member oligosaccharide, dichloroisoeverninic acid, and methyl eurekanate... 

The branched lactones 32-34, found in oligosaccharide antibiotics of the orthosomycin family88 were characterized as their methyl aldo-nates85 387-388 (253 - 255), and synthesized as follows. The introduction of... 

Complex glycosylated compounds like macrolides, anthracyclines, aureolic acids, cardiac glycosides, orthosomycines and tetronic acids are of considerable scientific as well as pharmaceutical interest. Obviously, each of them is responsible for certain therapeutic effects with respect to different diseases. Anthracyclines and aureolic acids are applied in cancer chemotherapy, orthosomycines are active as antibiotics against Gram-positive bacteria, and the cardiac glycosides are used in the treatment of cardiac insufficiency. 

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... 

Some members of the orthosomycins, a group of compounds known for their antibiotic activity, showed activity against intestinal nematodes [429], The nucleoside peptide aspiculamycin (250), isolated from Strepto-myces toyocaensis, at 50 mg/kg, completely eliminated Aspicularis tetra-ptera and Syphacia obvelata (pinworm) from the intestinal tract of infected mice [430]. The related compound (251) has been claimed to show nematocidal activity towards B. lignicolus [431]. Anthelmycin (252) (hikizimycin) has been found to be effective against pinworms, round-worms and whipworms [432]. 

The above title has been proposed for the oligosaccharide antibiotics, which include the eveminomicins, flambamycins, destomysins, avilamycin, curamycin, hygromycin, and related compounds. A review on orthosomycins has appeared. ... 

Other reviews or articles of general relevance to have appeared cover the oligosaccharide antibiotics of Ziracia which are of the orthosomycin class and include everninomycin water-soluble, lectin-binding hybrids of chitosan and sialic acid, made by the reductive coupling of a-NeuNAcOC6H4CHO-(p) with... 

Orthosomycin antibiotics have been extensively reviewed. ... 

The synthesis of the avobiose unit in avoparcin, of bioactive methyl oleonolate diglycosides, and of antifungal diosgenyl glycosides is mentioned in Chapter 3. The synthesis of antitumour glycosylamino-indoloquinolines is covered in Chapter 10, and the preparation of methyl a-D-evalopyranoside, present in orthosomycin antibiotics, is referred to in Chapter 14. 

The gem -dlhalo compound (15). reported last year, c in be used as a precursor of orthoesters (Scheme 4). including spiro -bicyclic systems similar to those found in the orthosomycin antibiotics. 

Conventional transformations on 4-C -hydroxymethyl and 4-C-a-ihydroxyethyl branched-chain sugar precursors have served to prepare the L-idonate and D-galactonate derivatives (19) and (20) respectively, thereby confirming the structures of 2,3-0-methylene-ald-onolactones present in orthosomycin antibiotics. Yoshimura s group have also confirmed the structure of the naturally occurring... 

The methyl glycoside of curacin (49)(the chromophoric terminus of several orthosomycin antibiotics) has been prepared as shown in... 

The synthesis of a trisaccharide fragment of some orthosomycin antibiotics is referred to in Chapter 3. 

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