Amphidinolide X, a Novel 16-Membered Macrodiolide from Dinoflagellate Amphidinium sp.

Abstract

A novel cytotoxic 16-membered macrodiolide, amphidinolide X (1), has been isolated from a marine dinoflagellate Amphidinium sp. (strain Y-42). The gross structure of 1 was elucidated on the basis of spectroscopic data including one-bond and long-range (13)C-(13)C correlations. The relative and absolute stereochemistries were determined by combined analyses of NOESY data and (1)H-(1)H and (1)H-(13)C coupling constants of 1 and NMR data of the degradation products. Amphidinolide X (1) is the first macrodiolide consisting of polyketide-derived diacid and diol units from natural sources. The biosynthetic origins of 1 were investigated by means of feeding experiments with (13)C-labeled acetates.

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…Other synthetic highlights included a cross-metathesis to couple the C1−C7 and the C8−C12 fragments, an esterification to introduce the dipeptide unit and a macrolactamization to build the macrolide core (Scheme 132). 306 The stereocontrolled convergent synthesis of amphidinolide X, a cytotoxic macrolide isolated from Amphidinium dinoflagellates, 307 reported by Rodríguez-Escrich, Urpí, and Vilarrasa included a stereoselective crotylation of the monoketal-protected acetylacetaldehyde with the chiral crotyltitanium reagent (S,S)-22b to established the stereochemistry at C10 and C11. The anti-isomer was obtained in this way in 80% yield, taking place a Re-face addition taking place (Scheme 133).…”

“…339 Interestingly, amphidinolide X is the only naturally occurring macrodiolide known to date that consists of a diacid and a diol unit rather than of two hydroxyacid entities. 307 Furstner and coworkers performed a convergent stereoselective synthesis of this natural product, and one of the building blocks was accessed by addition of the allenylzinc reagent resulting from the mesylate of (S)-3-butyn-2-ol, upon palladium-catalyzed reaction with Et 2 Zn, to the monoacetal of acetylacetaldehyde. The anti isomer was the major component of the reaction mixture (4.5:1 dr) in 65% yield, the nucleophilic addition of the allenylzinc to the Re-face of the carbonyl group taking place (Scheme 151).…”

Stereochemical analysis of α1, a mating hormone of the phytopathogen Phytophthora

“…Although some examples of simple alcohols (R = alkyl) 8,9 and a d-hydroxy compound (R = R 0 CH(OH)-) 10 are already known, the absolute configuration of d-oxo compounds (R = R 0 CO-), such as a1 1 has not been examined. Therefore, a model compound that possesses the same substructure (C-1 to C-6) as that of 1, (S)-1-hydroxy-3-methyl-4-octanone 3, was synthesized (Scheme 1).…”

Expedient Synthesis of (−)‐Amphidinolide X

“…(−)‐Amphidinolide X ( 1 , Scheme ) is one of the cytotoxic macrolides isolated by Kobayashi and co‐workers from the laboratory‐cultured dinoflagellates Amphidinium sp., which are symbionts of the Okinawan marine flatworms Amphiscolops sp 1. Amphidinolide X ( 1 ) is known to possess cytotoxic activity with IC 50 values of 0.6 and 7.5 μg mL −1 against murine lymphoma L1210 and human epidermoid carcinoma KB cells, respectively, in vitro.…”