rac‐altersolanol A and related tetrahydroanthraquinones, total synthesis and cytotoxic properties

Abstract

h key step in the lirst synthesis of racemic altersolanol A ( l a ) is rlic regiosclcctivc Diels-Alder reaction of 5-acetoxy-7-methoxy-1.4-naphtlioyuinone (12) with 2-methyl-l-(trimethylsiloxy)-1.3-hutadicnc (13) 10 afTord ihc adduct 14. Thc structure of 14 has hccn confirmed by X-ray mcasurcmcnts. The hydroxy groups of ring A arc introducod hy cpoxidation of 14 to 20, rearrangement t o the allylic ;ilcohol 26, epoxidation to 31, and opening of the iwiranc to rtrc~-altcrsolanol A (1 a). Similar products were obtained stwting from juglonc (15). Many ofthc intermediate cpoxidcs and also compounds 42 -44 show remarkable cytotoxicity in all culturcs hut all conipounds were too toxic to be useful as anticancer apcnts.Altersolanol A (1 a) (identical with stemphylin and altersolanol B (lb), dactylariol(2) and bostrycin (4a) are closely related tetrahydroanthraquinone antibiotics that occur in various species of f~n g i~-~) .Recently two related pigments, austrocortilutein (3) and austrocortirubin (4 b) from the subgenus Derrrzocybe of Cortinarius, were also isolated6). The names of the antibiotics are related to their origins in Alternaria solani7>'), Dactylaria lutes'), and Bostrychonema alpstre") ( naphthazarin to related tri-and tetracyclic quinone antibiotic~'~'.We now describe the first total synthesis of racemic la, in which a similar strategy for the construction of the tetra-

Total Synthesis of Premithramycinone H and Related Anthrapyran Antibiotics

“…The exclusive formation of the required monomethoxy diester 14a was achieved when the corresponding mixed tert-butoxy-OTMS ketene acetal was used in the DielsϪAlder reaction, as previously observed in related reactions. [26] Silylketene acetals are very often used in DielsϪAlder reactions. [27] The use of the tert-butoxy-OTMS ethers such as 12b for selective synthesis of phenols (instead of mixtures with methyl ethers) is therefore of general importance for DielsϪAlder reactions with ketene acetals.…”

“…13 C NMR (50 MHz, CDCl 3 ): δ ϭ 0.7 (q, 3 ϫ CH 3 ), 54.5 (q, OCH 3 ), 55.4 (q, OCH 3 ), 76.0 (d, C-2), 79.0 (t, C-4), 159.1 (s, C-1, C-3) ppm. -3-methoxy-1-(trimethylsilyloxy)buta-1,3-diene (12b): [40] Starting material tert-butyl 3-methoxybut-2-enoate (13.0 g, 75.6 mmol) afforded 12b (17.9 g, 73.3 mmol, 97 %) as a colorless oil. 13 …”

New Anthracene Derivatives – Structure Elucidation and Antimicrobial Activity

“…The two new heterodimers differ in the linkage of their monomeric building blocks. Compounds 1 and 5a were found to be structurally related to altersolanol A (5), [6][7][8][9] likewise isolated from S. globuliferum.…”

Absolute stereochemistry of altersolanol a and alterporriols

“…NMR spectra were measured on a JEOL ALPHA 400 and a JEOL JNM-ECX500 spectrometer. The chemical shifts for 1 H NMR in CDCl 3 are expressed in ppm downfield from the signal of tetramethylsilane used as an internal standard. The signal 13 CDCl 3 (77.0 ppm) was used as the standard in 13 C NMR in CDCl 3 .…”

“…We found that the dimerization of 1 in vitro gave a pair of atropisomers 2 and 3, which must have identical configuration on their central chirality elements, id est, tetraol moieties. The axial stereochemistry was studied by chemical derivatization in combination with 1 H NMR spectroscopic analyses. This was confirmed by comparison of the experimental and theoretical CD spectra.…”