Chemistry of zamoranic acid. Part V Homochiral semisyntheses of active drimanes: Pereniporin B, polygodial and warburganal

From Labdanes to Drimanes. Degradation of the Side Chain of Dihydrozamoranic Acid.

“…Among the natural antifeedants, azadirachtin isolated from Azadirachta indica [4], some clerodane diterpenoids such as jodrellin A and B isolated from Schutellaria woronowii Juss [5] and some drimanes such as warburganal (2b) isolated from Warburgia ugandensis [6] and polygodial (2a) isolated from Polygonum hydropiper [7] should be highlighted because their specific and high antifeedant activity against Spodoptera species [8], which causes more than 30% crop losses in India [9]. In our lab several bioactive drimanes ( Figure 1) have been synthetised starting from zamoranic acid [10]. …”

Oxidative Degradations of the Side Chain of Unsaturated Ent-labdanes. Part II

“…The stereochemistry assigned to the C-8 carbon was indirectly deduced from gs-sel-1 H 1D-NOESY correlations experiments; long range interactions between H-12α with H17b and H-17a with Me-20 were observed, therefore suggesting the stereochemistry at C-8 (see Figure 2b). Because under these conditions (K 2 CO 3 /MeOH) it was not possible to obtain the desired compound, we then focused on attempting the opening of the epoxide ring with HIO 4 , according to a method previously described for other oxirane rings [20,21]. Under these conditions, we hoped to generate a diol function between the C-8 and C-17 carbons, which by subsequent treatment with Pb(OAc) 4 in benzene [22], would give the desired ketone group at C-8.…”

A mild Lewis acid mediated epoxy-ester to bicyclic ortho ester rearrangement

“…9 The chemistry was further used in the semisynthesis of bioactive drimanes, pereniporin B and warburganal, but no follow up on the ortho ester chemistry. 10 We believe this reaction warrants further exploration since ortho ester remain an under exploited functional group in organic chemistry, thus giving 35 access to unusual compounds and opens up the development of new chemical space. Herein we report our preliminary studies.…”

“…Some variations in the diastereoselectivity was seen with ZnBr 2 depending on the reaction conditions while Yb(OTf) 3 giving essentially one diastereoisomer. The chlorinated solvents DCM and DCE appear 10 to be best solvents for this reaction and it typically ran smoothly at room temperature over a period 8 hours. The scope of this ortho ester formation reaction was then explored using a range of epoxy ester substrates.…”

“…There have been numerous reports on the rearrangement of epoxy-ketones into dioxabicyclo[3.2.1]octanes which is related to our ortho ester rearrangement chemistry.11 The rearrangement precursor (17) would serve as the ideal 5 starting material to determine whether the ester carbonyl or the ketone carbonyl would be more reactive under the Lewis acid rearrangement reaction condition. It was prepared as a pair of inseparable diastereomers (17a-b) by alkylation of ethyl acetoacetate with 4-bromo-1-butene, followed by epoxidation 10 with mCPBA. Reaction between the ester and the epoxide will give the ortho ester, otherwise reaction between the ketone and the epoxide will give the ketal product.…”