TY - JOUR
T1 - Steroids and related natural products. Part XCI. Synthesis of the cardenolides canarigenin and uzarigenin
AU - Kamano, Yoshiaki
AU - Pettit, George
AU - Tozawa, Machiko
N1 - Funding Information:
Uzarigenin (12 mg),m.p. 246-248" (from chloroform-methanol-hexane), wasisolated as described for reduction with lithium borohydride.Both synthetic samples were identical with a sample kindlyprovided by Dr. Haede.*Treatment of uzarigenin (Ic) (30 mg) with acetic an-hydride (0.45 m1)-pyridine (0.6 ml) for 18 h a t room tem-perature and recrystallization of the crude acetate frommethylene chloride-hexane led to uzarigenin 3p-acetate(24 mg), m.p. 265-268" (lit.,9 266-267'); m/e 416 (M+),398 (M+ - H20), 356 (M+ - AcOH), and 338 (M+ -Uzarigenone (IVd) [14-Hydroxy-3-oxo-5cc, 14P-card-20(22)-enolide] .-(A) By use of N-bromoacetarnide. Oxidation ofuzarigenin (Ic) (20 mg) with N-bromoacetamide (25 mg) inmethanol (3.5 m1)-acetone (2 m1)-water (0.1 ml) a t roomtemperature during 22 h was carried out as described forthe preparation of the ketone (IVa). The product waspurified by column chromatography and the fractioneluted with 5 : 1 hexane-acetone was recrystallized frommethylene chloride-methanol to yield uzarigenone (IVd)(12 mg), m.p. 269-272' (lit.,9 270-273') (Found: C,74.25; H, 8.7. Calc. for C23H320,: C, 74.15; H, 8.65%);t.1.c. RF 0.18; 8 (10% in CDCl,) 0.89 (3 H, s, 18-H3),1.01 (3 H, s, 19-H,), 2.79 (1 H, d, J 8 Hz, 17a-H), 4.80 and5.00 (2 H, slightly doubled AB-type q, J 17 and 2 Hz,21-H,), and 5.88 (1 H, t, J 2 Hz, 22-H); m/e 372 (M+)and 354 ( M f - H20).(B) By use of chromium trioxide. The ketone (IVd)AcOH - HaO).* See footnote p. 19731976 J.C.S. Perkin I(12 mg) (m.p. 209-273') was obtained by oxidizing also acknowledge financial support from the J. W. Kieck-uzarigenin (Ic) (20 mg) with chromium trioxide (13 mg) in hefer Foundation, the Fannie E. Rippel Foundation, theacetic acid (3 ml). Arizona Public Service Co., The Salt River Project ofArizona. and Mrs. Virginia Bayless.This investigation was supported by a Public HealthResearch Grant from the National Cancer Institute. We [6/143 Received, 22nd January, 1976
PY - 1975
Y1 - 1975
N2 - From 3β,14-dihydroxy-5β,14β-card-20(22)-enolide (digitoxigenin)(III), new formal total syntheses of canarigenin [3β,14-dihydroxy-14β-carda-4,20(22)-dienolide](IIa) and uzarigenin [3β,14-dihydroxy-5α,14β-card-20(22)-enolide](Ic) have been completed. The route found most convenient involved direct oxidation of digitoxigenin (III) with t-butyl hypochlorite to yield the 4β-chloro-3-ketone (IVb). Dehydrohalogenation to the 4-en-3-one (canarigenone)(V) was followed by selective reduction with lithium hydrido-tri-t-butoxyaluminate to afford canarigenin (IIa) and with lithium borohydride to yield uzarigenin (Ic).
AB - From 3β,14-dihydroxy-5β,14β-card-20(22)-enolide (digitoxigenin)(III), new formal total syntheses of canarigenin [3β,14-dihydroxy-14β-carda-4,20(22)-dienolide](IIa) and uzarigenin [3β,14-dihydroxy-5α,14β-card-20(22)-enolide](Ic) have been completed. The route found most convenient involved direct oxidation of digitoxigenin (III) with t-butyl hypochlorite to yield the 4β-chloro-3-ketone (IVb). Dehydrohalogenation to the 4-en-3-one (canarigenone)(V) was followed by selective reduction with lithium hydrido-tri-t-butoxyaluminate to afford canarigenin (IIa) and with lithium borohydride to yield uzarigenin (Ic).
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U2 - 10.1039/P19750001972
DO - 10.1039/P19750001972
M3 - Article
C2 - 1238419
AN - SCOPUS:0016647353
SP - 1972
EP - 1976
JO - Journal of the Chemical Society, Perkin Transactions 1
JF - Journal of the Chemical Society, Perkin Transactions 1
SN - 1470-4358
IS - 19
ER -