Joalin, the first nitrogen-containing xenicane diterpene isolated from a brown seaweed collected off the Senegalese coast

Journal of the Chemical Society, Perkin Transactions 1
1993.0

Abstract

Joalin (-)-1, isolated from the brown seaweed Dictyota sp. collected off the Senegalese coast, is the first nitrogen-containing xenicane diterpene. Brown seaweeds of the order Dictyotales, sea hares, and alcyonaceans produce numerous nitrogen-free xenicane diterpenes, with only aminocembranolides from a tropical alcyonacean as an exception, contrasting with nitrogen-containing diterpenes from sponges of the orders Axinellida and Haplosclerida. The MeOH extract of Dictyota sp. was subjected to extensive chromatography to yield joalin (-)-1, whose molecular formula C21H31NO3 was determined by mass and 13C NMR spectroscopy. 1D (differential double irradiations) and 2D (COSY 120) 1H NMR spectra revealed three unsaturated positions (one tetra-substituted and two tri-substituted C=C bonds), and an amide/lactam carbonyl group (δC 174.60 (s)) confirmed by IR absorption (v 1702s cm-1) and HREIMS (nitrogen presence), indicating a tricyclic structure. NMR correlations (HMQC, HMBC) established connectivity: oxygen substitution at C-4, an allylic methoxy group at C-9, C-18 bound to both N and O, a C5 isoprenic side-chain (supported by [M-69]+ EIMS fragment ion and 1H-1H COSY), and the C(5)-C(8) portion (from coupling of 7-H with 3×20-H and 8-Hβ, and 8-Hβ with 9-H). Long-range H-13C heterocorrelations (H(4)-C(5), H(9)-C(1)) joined the C(9)-C(1)-C(4) and C(5)-C(8) moieties into the flat structure (-)-1. NOE (7-H/3-H, 4-H/3×17-H) and coupling constants (small 9-H adjacent couplings, 3-H/4-H dihedral angle ~90°) determined the relative configuration and preferred conformation (1a), with unique features of nitrogen incorporation and chirality at C-9. Chiroptical data (CD Cotton effects: Δε259 +5.8, Δε275 -39.6 in CDCl3) suggested the absolute configuration 3S,4R,9R,10R,18R, consistent with other algal xenicanes; with caveats about extrapolation, (-)-1 represents joalin's absolute configuration. Joalin differs from known xenicanes by high J3,10 1H-1H coupling (10.4 Hz vs. ~0 in dictyolactone), attributed to 17-Me orientation opposite the lactam ring (molecular mechanics calculations). Its C-4/C-18 oxygen bridge precedes only in dictyotalide (from Okinawan Dictyota dichotoma). A biosynthetic route is proposed: a precursor with C-19 carboxy group → C-19 amide formation → enzyme-driven amide nitrogen attack on C-18 aldehyde → aminoketalization by 4-OH.

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