Amphidinolide Y, a Novel 17-Membered Macrolide from Dinoflagellate Amphidinium sp.:  Plausible Biogenetic Precursor of Amphidinolide X

Abstract

A novel cytotoxic 17-membered macrolide, amphidinolide Y (1), has been isolated from a marine dinoflagellate Amphidinium sp., and it was elucidated to exist as a 9:1 equilibrium mixture of 6-keto- and 6(9)-hemiacetal forms (1a and 1b, respectively) on the basis of 2D NMR data and chemical means. The feeding experiments with (13)C-labeled acetates suggested that amphidinolide Y (1) may be a biogenetic precursor of 16-membered macrodiolide, amphidinolide X (2).

Biosynthetic Study of Amphidinin A and Amphidinolide P

“…The methylenes at C-10 of amphidinolide T1 and C-17 of amphidinolide Y were the rare case for the carbon originated from C-2 of cleaved acetate. 13,15) This hypothesis does not contradict the idea that the addition of branched C 1 unit to C-2 of cleaved acetate was also done by HCS cassette.…”

“…[2][3][4][5][6][7] The carbon skeletons of dinoflagellate polyketides are unique and unavailable from other organisms, since they might be generated by unexplained one-carbon extension machinery in addition to the ordinary polyketide biosynthesis. 8) In our continuing biosynthetic study of dinoflagellate polyketides, [9][10][11][12][13][14][15][16] we have recently re-isolated amphidinin A (1) 17,18) and amphidinolide P (2) 19,20) from the cultured marine dinoflagellate Amphidinium sp. (2012-7-4A strain) which were isolated from an acoel flatworm Amphiscolops sp.…”

New Derivatives of Levoglucosan by Tandem Epoxide Allyl Alcohol Rearrangement‐Cuprate Cross‐Coupling

“…It is noteworthy that the advantage of this anhydrosugar based "chiral pool" approach may reside in the construction of unusual substitution patterns rather than the 1,3-sequence of methyl and hydroxy groups found in "normal" polypropionate-derived natural products. For example, the substitution pattern and the (2S,3R) stereochemistry of compound 11 is present in more than 100 polypropionate-derived com-pounds, including lankanolide, [38] amphidinolide, [39] the large groups of erythronolides, [40] and the cytochalasins (Scheme 3). [41] Scheme 3. a) PDC, CH 2 Similarly as performed for the saturated derivative 10, the stereochemical outcome of the reactions of the unsaturated ketone 9, and the allyl acetates 6b and 15 were investigated.…”

“…24 h) the solution was diluted by addition of diethyl ether (500 mL), the precipitate filtered off (Celite, washed with diethyl ether, 100 mL), and the filtrate was evaporated at reduced pressure. The residue was purified by flash chromatography (CH 2 Cl 2 /acetone, 100:0 to 98:2) to obtain ketone 9 (5.5 g, 39 q, C-8 Acetyl-1,6-anhydro-2,3-dideoxy-2,4-dimethyl-β-D-threo-hex-2enopyranose (15): A solution of 14 (620 mg, 3.97 mmol in anhydrous CH 2 Cl 2 (20 mL) was acetylated at 0°C by addition of triethylamine (2.1 mL, 15.6 mmol), Ac 2 O (1.6 mL, 15.6 mmol), and DMAP (cat.). After 1 h the solution was warmed to 20°C and was kept at that temperature for an additional 5 h, and was then quenched by pouring into ice-water.…”

Generation of Molecular Shape Diverstiy. From Privileged Scaffolds to Diverted Total Synthesis

“…. Many of these macrolides exhibit strong cytotoxicity against murine lymphoma L1210 and human epidermoid carcinoma cell lines.Figure 4shows the structures of amphidinolide T1-T5(19)(20)(21)(22)(23) [97][98][99], X (24)[100], and Y (25)[101]. Except for the C21 stereogenic center on the side chain, amphidinolide T2(20) shares the same macrolactone core as amphidinolide T3(21)while amphidinolide T1 and T3-T5 only differ in the regio-and stereo-chemistry at C12-C14.…”