Siastatin

Siastatin A and B were isolated by Umezawa et al in 1974 from a Streptomyces cnl-ture Streptomyces verticillus var. qnintnm MB695-A4). Siastatin B was found to inhibit neuraminidases. It is involved in various biological functions such as immune response, 

The first total synthesis of siastatin B (1) was achieved from L-ribose by protection of the 2,3-diol, followed by introduction of an azide group on C-5 and oxidation of the anomeric hydroxyl group to give 5-azido-5-deoxy-2,3-0-isopropylidene-L-ribonolactone 

Nishimura, Y. Institute of Microbial Chemistry, Tokyo, Japan. Personal communication, 2004. 

Nishimura, Y Umezawa, Y Kondo, S. Takeuchi, T. Mori, K. Kijima-Suda, L Tomita, K. Sugawara, K. Nakamura, K. J. Antibiot. 46 (1993) 1883. 

Nishimura, Y. InStudies inNatural Products Chemistry, Vol. 16 Atta-ur-Rahamn, Ed. Elsevier Amsterdam, 1995 p. 75. 

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H. Umezawa, T. Aoyagi, T. Komiyama, H. Morishima, M. Hamada, and T. Takeuchi, Purification and characterization of a sialidase inhibitor, siastatin, produced by Streptomyces, J. Antibiot., 27 (1974) 963-969. 

Siastatin B (40), the first natural inhibitor of neuraminidase and a compound that also inhibits -D-glucuronidase, was discovered in 1974 [139]. Two total syntheses of this compound have been published to date [140,141]. Due to the fact that recent studies have shown that human tumours are associated with... 

Neuraminidase Inhibitors — Siastatin B and Derivatives. Siastatin B, which can be regarded as a glycosyl acetamide of a branched chain 5-amino-5-deoxypentose, was isolated from a Streptomyces culture [204] and was subsequently shown, by total synthesis, to be 77 (Figure 9.24) [205]. 

In the piperidine series, apart from the above-mentioned antibiotic nojirimycin 1, siastatin 77 and derivatives thereof exhibit activity against bacterial neuraminidases, such as the enzymes from Clostridiumperfrigens, with an IC50 of 18 p-g/ml, and Streptococcus sp. with 6.3 pg/ml [206,207]. 

Nishimura, Y, Wang, W, Kondo, S, Aoyagi, T, Umezawa, H, Siastatin B, a potent neuraminidase inhibitor the total s3mthesis and absolute configuration, J. Am. Chem. Soc., 110, 7249-7250, 1988. 

N-(1,2Dihydroxypropyl)-siastatin B 1C50 = 1.0x10-5-2.7x10-5 bacterial [873]... 

The A -allyllactam 119 was converted by RCM to 120, which on catalytic osmylation provided the polyhydroxylated indolizidine 121 <04OBC3128>. An analog 122 of the iminosugar siastatin B was prepared from the tetrahydropyridine 123. The relative configuration of the substitiuents in the latter were defined by the RCM reaction precursor 124 derived from a 2-azetidinone <04SL2776>. 

The L-iduronic acid-like 1-iV-imino sugars 39-41 have been prepared from a siastatin B derivative (See Vol. 27, p. 237, ref. 96) as metastasis inhibitors. The synthesis and glycosidase activity of other siastatin B analogues are mentioned in Chapter 19. 

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