The oxidation of methyl (+)-13β-abiet-8-en-18-oate with Collins reagent yielded nine oxidation products. Their structures were elucidated on the basis of spectroscopic and chemical data to be methyl (−)-14-hydroxy-7-oxoabieta-8,11,13-trien-18-oate (1% yield), methyl (−)-11,14-dioxoabieta-8,12-dien-18-oate (1%), methyl (+)-11-oxo-13β-abiet-8-en-18-oate (18%), methyl (−)-8α,9α-epoxy-7-oxo-13β-abietan-18-oate (2%), methyl (+)-7-oxoabieta-8,11,13-trien-18-oate (2%), methyl (+)-11,14-dihydroxy-7-oxoabieta-8,11,13-trien-18-oate (2%), methyl (+)-7,11-dioxo-13β-abiet-8-en-18-oate (17%), methyl (+)-14-oxo-13β-abiet-8-en-18-oate (15) (4%), and methyl (+)-7-oxo-13β-abiet-8-en-18-oate (23%) respectively. It is noteworthy that oxygenation occurs not only at the C-7 and C-11 positions but also at the C-14 position. The oxygenated products obtained in this studies could be useful intermediates for the synthesis of the oxidized diterpenoids of abietane skeleton. To exemplify this, 15 was converted to methyl suaveolate and suaveolol. Hydrolysis of the former yielded suaveolic acid, thus confirming its absolute configuration to be 4R, 5R, 10S, 13S, and 14S.

Oxidation of 11-acetoxyabieta-8,11,13-triene, derived from methyl 11-methoxyabieta-8,11,13-trien-18-oate, with chromium trioxide afforded 11,15-diacetoxyabieta-8,11,13-trien-7-one and 11-acetoxy-13-acetylpodocarpa-8,11,13-trien-7-one (11) in a ratio of ca. 2 : 1. The acetyl compound 11 was converted into a quinone, 13-(hydroxymethyl)podocarpa-8,12-diene-11,14-dione (18), by a series of reactions : iodoform reaction, esterification, acetylation, sodium borohydride reduction, dehydration, catalytic hydrogenation, lithium aluminium hydride reduction, and oxidation with Fremy’s salt. Reductive acetylation of 18 produced 11,14-diacetoxy-13-(acetoxymethyl)-podocarpa-8,11,13-triene (2). The 1H NMR spectrum of 2 was different from that of 15-acetoxypremnol diacetate which was prepared from natural premnolal. Based on this fact a corrected structure of premnolal is proposed.

Die Synthese der Titelverbindung, Bestandteil von Premna latifolia Roxb.

The revised structure of premnolal was confirmed by the following synthesis. Treatment of 12-methoxypodocarpa-8,11,13-triene (7), derived from methyl 12-methoxypodocarpa-8,11,13-trien-18-oate, with ethoxyoxalyl chloride and anhydrous aluminium chloride afforded 13-(ethoxyoxalyl) derivative, which was converted into 12-hydroxypodocarpa-8,11,13-triene-13-carbaldehyde (9) by alkaline hydrolysis, decarboxylation, and demethylation. The compound 9 was also prepared from 7 by demethylation and formylation. Reduction of 9 with lithium aluminium hydride, followed by partial acetylation, afforded 13-acetoxymethyl derivative which was converted into 13-acetoxymethyl-12-methoxy-11-nitropodocarpa-8,11,13-triene by nitration and methylation. This was then converted into 11,12-dimethoxypodocarpa-8,11,13-triene-13-carbaldehyde (18) by a series of reactions: catalytic hydrogenation, diazotization, reduction with lithium aluminium hydride, methylation, and oxidation. Demethylation of 18 gave 11,12-dihydroxypodocarpa-8,11,13-triene-13-carbaldehyde, which was identical with natural premnolal.

Treatment of methyl (+)-11-oxo-13β-abieta-8-en-18-oate with copper(II) bromide and lithium bromide afforded the corresponding phenol derivative, which was methylated to methyl 11-methoxyabieta-8,11,13-trien-18-oate (7). The same compound was also prepared from methyl (+)-7,11-dioxo-13β-abieta-8-en-18-oate via methyl 11-hydroxy-7-oxoabieta-8,11,13-trien-18-oate, its methyl ether, and methyl 11-methoxyabieta-6,8,11,13-tetraen-18-oate. The Grignard reaction of 7 with phenylmagnesium bromide followed by treatment with lead tetraacetate and subsequent oxidation with selenium dioxide afforded 11-methoxy-19-norabieta-4(18),8,11,13-tetraen-3α-ol (12), which was converted to 11-methoxy-19-norabieta-8,11,13-trien-3-one (20) by catalytic hydrogenation, Jones oxidation, and isomerization. The compound 20 was also obtained by Birch reduction of 11-methoxy-19-norabieta-4,8,11,13-tetraen-3-one prepared from 12  via 11-methoxy-19-norabieta-4,8,11,13-tetraen-3α-ol. Subsequently, the compound 20 was transformed to 11-methoxyabieta-1,8,11,13-tetraen-3-one (27) by a series of reactions: acetalization, demethylation, hydrolysis, acetylation, bromination, dehydrobromination, and methylation. Finally, the compound 27 was converted to the title compound, (+)-11-hydroxyabieta-2,8,11,13-tetraen-1-one (1), by oxidation with alkaline hydrogen peroxide, heating with hydrazine hydrate, Jones oxidation, and demethylation. Although the synthetic (+)-1 was shown to be different from natural shonanol, the spectral analyses of the synthetic structural isomers showed the structure of shonanol to be 12-hydroxyabieta-2,8,11,13-tetraen-1-one.