Fluvirucin A1

Fluvirucin A1 was established as (2R,3S,6R, 10S)-3-[(3-amino-3,6-dideoxy-alpha-L-talopyranosyl)-oxy]-2,6-dimethyl-10 -ethyl-13-tridecanelactam by chemical, spectroscopic, and X-ray crystallographic analyses.

The morphology, chemotaxonomy, and cultural and physiological characteristics were examined on the five strains of actinomycetes which produce antiviral antibiotics, fluvirucin congeners. All strains have meso-2,6-diaminopimelic acid in the cell wall. Four strains, Q464-31, L407-5, R359-5 and R516-16, belong to the maduromycetes since they have madurose in the whole cell. The remaining one strain, R869-90, has rhamnose but no madurose, and is a nocardioform actinomycete. These five strains were classified and designated as follows: Strain Q464-31 (fluvirucin A1 producer): Microtetraspora tyrrhenii sp. nov. (Actinomadura pusilla group). Strain L407-5 (fluvirucin B2 producer): A maduromycete. Strain R359-5 (fluvirucin B1 producer): Microtetraspora pusilla (Actinomadura pusilla group). Strain R869-90 (fluvirucin A2 producer): Saccharothrix mutabilis. Strain R516-16 (fluvirucins B2, B3, B4 and B5 producer): A maduromycete.

ZACA-lipase-catalyzed acetylation tandem process has been shown to proceed satisfactorily with either TBS-protected 4-penten-1-ol or 3-buten-1-ol to provide the corresponding enantiomerically pure (R)-2-ethyl-1-alkanols. Either (R)-5 or (R)-6 was converted to 3 in seven steps. The other fragment 4 was synthesized in nine steps from (-)-(S)-citronellol. Conversion of 3 and 4 into 99% pure fluvirucinine A1 was achieved in four steps via amidation-ring closing metathesis, the overall yield in the longest linear sequence being 34% (13 steps).