The Synthesis of Lycoxanthol and Its C-15 Epimer

Abstract

In order to elucidate the absolute configuration of C-15 in natural lycoxanthol, (15R)-11,16-dihydroxy-12-methoxymethoxy-8,11,13-abietatrien-7-one and its (15S)-epimer were transformed into (15R)-12,16-epoxy-6,11,14-trihydroxy-5,8,11,13-abietatetraen-7-one (1a) and its (15S)-epimer, respectively. The synthetic 1a was identical with natural lycoxanthol. Thus, the stereochemistry of C-15 in the natural compound was conclusively assigned as R-configuration.

Approaches to the Synthesis of Aromatic Diterpenes Oxygenated in Ring A: Synthesis of Margocilin O-Methyl Ether

“…The final products in the coleon B synthesis were chemically interesting but had only been obtained in modest yield, and since these same reactions could also be the final steps in the preparation of coleon E, the efficiency of a variety of reagents was com- {Vol. 56, No. 4 pared to effect the allylic oxidation at C-2 in the conjugated dienone 3a [easily prepared from 2a (3)].…”

“…Stirring was continued for 26 h, and the mixture was then poured into dilute HC1 (5%, 1 liter). The Et20 extract was washed with dilute HC1, H20, and aqueous NaOH, and after drying and concentration the residue was chromatographed [petroleum ether-Et20 (10:1)] to give the acetyl derivative 21c (5.20 g, 21%), 3-acetyl-4-methoxyphenypropyl acetate: it (neat) 1740, 1675, 815 cm"1; 'H nmr 1.90 (m, 2H, H-6), 2.04 (s, 3H, AcO), 2.59 (s, 3H, MeCOAr), 2.70 (m, 2H, H-7), 3.87 (s, 3H, MeO), 4.04 (t, 2H, 7=6.2 Hz, H-5), 6.88 (d, 1H,7= 8.4 Hz), 7.26 (dd, 1H,7= 8.4 and 2.2 Hz), 7.55 (d, 1H,7 = 2.2 Hz); ms mtz [M]+ 250 (12), 235 (15), 191 (5), 177 (8), 175 (100), 163 (24). Exact mass caled for C14H1804, 250.1205; found 250.1206.…”

“…Acidification of the NaOH washings from above and extraction with Et20 afforded the corresponding phenol 21d (0.349 g, 40%), 4-hydroxy-3-acetylphenylpropyl acetate: 'H nmr 1.90 (m, 2H), 2.03 (s, 3H), 2.59 (s, 3H), 2.70 (m, 2H), 4.08 (t, 2H,7 = 6.6 Hz), 6.87 (d, 1H,7=8.4 Hz), 7.27 (dd, 1H, 7 =8.4and2.2 Hz), 12.09(s, 1H,dis. D20);msro/z[M]+ 236 (14), 221(2), 177(8), 163 (6), 161(100), 149 (44).…”

“…7 Hz, H-ll), 7.00 (d, 1H,_/ = 8. 4 Hz, H-14). Exact mass caled for Cl8H2402, 272.1776; found 272.1762.…”

“…Ideally, well-known natural substances such as dehydroabietic acid [1} and podocarpic acid [2a] are the most appropriate starting materials for such syntheses since they lead not only to functionally correct molecules but also to the enantiomerically proper structures. The publications of Cambie (1,2) have shown the versatility of these natural chirons, and Matsumoto and co-workers (3,4) have ably exploited their availability in many of their syntheses. 3b Ri=R2=H, R3=AcO 3c R'=0, R2=R3=H 3d R'=0, R2 = Br, R3 = H Following our syntheses of coleon B (5) as the tri-O-methyl ether and taxodione (6), it seemed logical to turn our attention to coleon E (7), which appears to contain a hybrid of the two chromophores.…”