THE STRUCTURE OF LATUMCIDIN (ABIKOVIROMYCIN) DETERMINED BY X-RAY ANALYSIS

The Journal of Antibiotics
1970.0

Abstract

Latumcidin (abikoviromycin), C₁₀H₁₁NO, is an optically active antiviral antibiotic isolated from the culture broth of Streptomyces reticuli var. latumcidicus and is highly unstable, promptly polymerizing during isolation. In 1968, A.I. Gurevich et al. reported its structure as (4S, 4aR) 5-ethylidene-2,3-dihydro-1,5-pyridine-4,4a-oxide via chemical methods. We attempted to confirm this structure using NMR and X-ray analysis. NMR of the free base in deuteriobenzene had uncertain assignments for the singlet at δ 3.49 and multiplet at δ 1.14, with decoupling studies unsuccessful. We crystallized the antibiotic as selenate (C₁₀H₁₁NO·H₂SeO₄, M.W. 306), which are colorless needles (m.p. 121°C dec), monoclinic (space group C2, four molecules per unit cell, a=26.07Å, b=4.87Å, c=9.66Å, β=95.05°). Intensities of 1392 independent reflections were measured (Cu Kα), and structure was solved via Patterson function (selenium location), Fourier/difference syntheses, and least-squares refinement (final reliability factor 9.5%). Absolute configuration was determined using anomalous dispersion of selenium (Cr Kα), revealing asymmetric carbons as 4(R) and 4a(S) — contradictory to Gurevich et al.'s (4S, 4aR) report. The NMR singlet at δ 3.49 was explained by ~60° bond angles (Karplus equation, near-zero coupling), and the δ 1.14 multiplet by axial C3 protons (equatorial at δ 1.75 in deuteriobenzene).

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