Siastatin synthesis

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]. 

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... 

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. 

D-Ribono-y-lactone is a convenient substrate for the synthesis of siastatin B analogues 35, including their enantiomers. Other analogues 36 have also been prepared, including ring nitrogen jV-alkyl analogues. 

In order to clarify its absolute stereochemistiy, both enantiomers of the naturally-occurring sialidase inhibitor siastatin B were prepared from the enantiomers of ribose in multistep sequences, and the natural product was shown to have structure (48), the carbons of the precursor L-ribose being indicated.Compounds (49, R=H and OBn) have been prepared from D-glucose (carbons indicated) as potential precursors for the pyrrolizidine alkaloids retroneclne and crotanecine respectlvely. S Some other references to the synthesis of hydroxylated pyrrolidines and piperidines appear in Chapter 18. 

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