Synthesis of N-containing drimane sesquiterpenoids from 11-dihomodriman-8α-ol-12-one

Abstract

Nitrogen-containing drimanes and their biological activity represent a poorly studied area of terpenoid chemistry. Therefore, the synthesis of such compounds is of scientific interest.The preparation of amides 1-4 via Beckmann rearrangement of the Z-and E-isomers of oxime 5 of 14,15-dinorlabd-8(17)-en-13-one (6) was reported earlier [1]. A multi-step synthesis of amide 7 from (-)-sclareol that uses the natural sesquiterpene drim-9,11-en-8D-ol (8) as an intermediate in the synthesis was described [2].Our goal was to study the synthesis of 7 via Beckmann rearrangement of oxime 9 of 11-dihomodriman-8D-ol-12-one (10). Hydroxyketone 10 is readily available and can be obtained from norambreinolide (11) by the method described by us [3]. Oxime 9 was prepared from 10 by reaction with NH 2 OHHCl in a mixture of EtOH and Py. It was a mixture of the Z-and E-isomers according to TLC and 1 H, 13 C, and 15 N NMR spectra. Because the Z-isomer can be easily converted to the E-isomer and the latter is energetically more favorable [1, 4], we used 9 for the reactions as a mixture of its Z-and E-isomers. The Beckmann rearrangement is known to occur stereospecifically as a result of anti-migration of the bulkier radical. Therefore, it was expected that the major product of the Beckmann rearrangement of 9 would be amide 7.

Synthesis of nitrogen-containing drimane sesquiterpenoids from 11-dihomodrim-8(9)-en-12-one

“…Oxime 6 (100 mg, 0.38 mmol) was treated with H 3 PO 4 (86%, 1 mL), heated at 70-75°C for 15 min until the oxime dissolved completely, heated at the same temperature for another hour, cooled in an ice bath, and treated dropwise with H 2 O (20 mL). The resulting white crystalline precipitate was filtered off, washed with H 2 O, dried in air, and recrystallized from hexane to afford a product (36 mg, 36%), mp 146-147°C, that had the same melting point and spectral characteristics as 1,2,6-oxazine (8) [7]. TLC used benzene:Et 2 O (1:2), R f 0.60.…”

“…A study of the reaction products of oxime 6 found that heating it at 70-80°C in H 3 PO 4 (86%) caused intramolecular cyclization to form (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1,2-e]-3-methyl-4,5-dihydro-[1,2,6]-oxazine (8), which we synthesized previously from 11-dihomodriman-8D-ol-12-one (1) [7], and (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1,2-d]-2-methylpyrroline-N-oxide (9) (Scheme 1). The structures of these compounds were confirmed by IR, 1 H NMR, and 13 C and 15 N spectral data and elemental analysis.…”

Synthesis of New Drimane and Homodrimane Lactams by Beckmann Rearrangement of Some Ketoximes

“…Then, Barrero et al described a multi-step synthesis of amide 7 from (-)-sclareol [7]. Later, amides 8 and 9 were synthesized by the Beckmann rearrangement of oxime 10 of 11-dihomodriman-8α-ol-12-one 11 [8] (Figure 1 The Beckmann rearrangement is known to occur stereospecifi cally as a result of anti-migration of the bulkier radical. Therefore, it has been expected that the major product of the Beckmann rearrangement of oxime 10 would be amide 7.…”

Synthesis of 12-amino-11-dihomodrimane Sesquiterpenoids from Norambreinolide

“…In continuation of our research on the synthesis of N-containing drimane and homodrimane sesquiterpenoids [6][7][8][9], herein we report the preparation of 12-amino-11-dihomodrim-8D-ol (5) and its dehydrated analogs 6 and 7 (Scheme 1).…”

“…They were used as the mixture of both isomers in the LiAlH 4 reduction because the Z-isomer is known to convert readily to the E-isomer in solution [11,12]. The spectral characteristics of oxime 9 [7], ketone 13 [8], and oxime 10 [8] were previously reported. Ketone 14 was first prepared in 7% yield in 1967 [13] via the reaction of hydroxyketone 12 with BF 3 H 2 O 2 and was not characterized spectrally.…”