Enantioselective synthesis of 11-homodrim-7-en-9α,12,13-triol

Abstract

The enantioselective synthesis of 11-homodrim-7-en-9D,12,13-triol, a convenient synthon for preparing polyfunctional 11-homodrimane sesquiterpenoids, was carried out starting from norambreinolide, a cleavage product available from several bicyclic labdane diterpenoids.One of the main motivators for the unwavering interest of chemists in drimane sesquiterpenoids is their broad spectrum of biological activity [1,2]. Several syntheses of them have been developed because most of them are difficultly accessible compounds and occur in trace quantities as complicated mixtures in natural sources [2][3][4]. However, many of the syntheses are multi-step and inefficient. In addition, the starting compounds are not always readily available.In contrast with drimane sesquiterpenoids, homodrimane (tetranorlabdane) compounds are more available because they can be prepared by relatively simpler methods from readily available labdane diterpenoids (sclareol, larixol, abienols, manool, manoyloxides, and zamoranic, communic, and labdanolic acids, etc.) [5].The preparation of tetranorlabdane derivatives has been often reported. Several of these derivatives have been widely applied in the perfume, cosmetic, and tobacco industries owing to their amber aroma. Judging from the literature, most homodrimanes have not been tested for types of activity other than organoleptic. However, it was recently found that 11-homopolygodial (1) had antifeedant activity greater than that of natural polygodial (2) [6]. Therefore, it seemed interesting to synthesize polyfunctional homodrimanes.Herein results from the synthesis of 11-homodrim-7-en-9D,12,13-triol (3) from commercially available norambreinolide (4) are reported.Norambreinolide (4) was reduced by LiAlH 4 by the literature method [7] to sclarodiol (5), which was identified by comparison with an authentic sample. Diol 5 was acetylated under standard conditions by a mixture of acetic anhydride and pyridine. According to TLC, the reaction products included the desired 12-monoacetate of sclarodiol (6) and an impurity of a less polar compound that was separated by chromatography over a column of SiO 2 (Scheme 1). Hydroxyacetate 6 was identified by comparison with an authentic sample that was obtained by us earlier [8]. Its spectral properties agreed with those published [9-10]. Reaction of 6 with triphenylphosphine and iodine by the literature method [11] formed a mixture of unsaturated acetates 7, in which the isomer with the tetra-substituted double bond dominated (64%) according to NMR spectroscopy. The contents of the isomers with the tri-substituted and exocyclic double bonds were 19 and 17%, respectively. Dehydration of 6 by phosphoryl chloride in pyridine afforded a product in which the isomer with the exocyclic double bond dominated [12]. The mixture of acetates 7 was oxidized by sodium chromate by the literature method [13] to 12-acetoxy-11-homodrim-8-en-7-one (8) (60% yield).Ketoacetate 8 was reacted with N-bromosuccinimide (NBS) in order to functionalize the C-13 methyl. This produced 12...

Synthesis of New Nitrogen-Containing Drimane and Homodrimane Sesquiterpenoids from Sclareolide

“…As starting material for the synthesis of the reported compounds methyl 7-oxo-13,14,15,16-tetranorlabd-8-en-12-oate 11 was used, obtained in two steps in 76% overall yield from the commercially available sclareolide 8 [9] (Scheme 1). Drim-8-en-7-one 12 can be obtained from ketoester 11 by known method as depicted in Scheme 1(a) as in [10].…”

Synthesis of Novel Tetranorlabdane Derivatives with Unprecedented Carbon Skeleton

“…4 So far, several syntheses of tetranorlabdanes have been performed based on ketoester 6. 5,9,12 This paper reports the continuation of our investigations 14,15 into the chemistry of (-)-sclareol (1) and describes new regio-and stereoselective syntheses of polyfunctional tetranorlabdanes (homodrimanes) starting from methyl 7oxo-13,14,15,16-tetranorlabd-8-en-12-oate (6).…”

“…In view of this, based on (-)-sclareol (1) and its derivative (+)-sclareolide (2), syntheses of important drimane sesquiterpenoids and some tetranorlabdanes have been performed via methyl bicyclohomofarnesoates 3-5 and methyl 7-oxo-13,14,15,16-tetranorlabd-8-en-12-oate (6, Figure 1). [3][4][5][6][7][8][9][10][11][12][13][14][15] Syntheses of tetranorlabdanes are generally shorter and easier than those of the related drimanes. Some of them have been applied on an industrial scale because the resulting tetranorlabdanes are used in perfumery, cosmetics, and tobacco products.…”