New Piperidine Alkaloids from Two Ladybird Beetles of the GenusCalvia (Coccinellidae)

Abstract

The alkaloids of two coccinellid beetles, Calvia14‐guttata and C.10‐guttata have been studied. The major alkaloid of these two species is the new piperidinic cis‐lactone 1a, for which the name calvine has been coined. The corresponding trans‐lactone 1b (2‐epicalvine) is also present as a minor constituent (±10%) in both species. We report here the structure determination and the total synthesis of these compounds. Kept in methanolic solution, these lactones undergo epimerisation as well as opening of the lactone ring leading to a complex mixture of nine main components.

Enantioselective Syntheses and Absolute Configuration of the Ladybird Defence Alkaloids (+)-Calvine and (+)-2-Epicalvine

“…The final steps of this synthesis are identical to those of our synthesis of racemic calvine. [6] An anodic oxidation carried out on (2S)-6 regioselectively furnished the 2-methoxylated compound (6S)-7 as a cis/trans mixture in 78% yield. Nucleophilic substitution of the methoxy function of (6S)-7 by 1-methoxy-1-trimethylsilyloxyethene [14] led to an 87:13 mixture of the carbamate esters (2S,6S)-8a and (2R,6S)-8b in 64% yield (74% de).…”

“…The cis configuration was assigned to the major stereomer by comparison of its 1 H NMR spectroscopic data and GC retention time with those of racemic 9a. [6] Hydroxyethylation of the mixture of (2S,6S)-9a and (2R,6S)-9b was achieved by treatment with an excess of ethylene oxide in methanol. As we previously observed, [6] this procedure led to the formation of a mixture of lactones 1a and 1b, methyl esters 10a and 10b, and byproduct 11.…”

“…[4,5] Recently, the alkaloids of two coccinellid beetles belonging to the genus Calvia have been investigated. [6] The major alkaloid from these two species is the piperidinic cis lactone (ϩ)-1a, which was named calvine. The corresponding trans lactone (ϩ)-1b (2-epicalvine) is also present as a minor constituent (about 10%) in both species.…”

“…The structure of these alkaloids has been determined on the basis of their spectral properties and confirmed by a total synthesis of racemic 1a and 1b. [6] In this paper, we wish to report two different enantioselective syntheses of (ϩ)-calvine [(ϩ)-1a] and (ϩ)-2-epicalvine [(ϩ)-1b], which allowed us to assign the absolute configuration (2S,6S) to natural (ϩ)-calvine and (2R,6S) to natural (ϩ)-2-epicalvine.…”

“…Synthetic strategies for (ϩ)-calvine (1a) and (ϩ)-2-epicalvine (1b) 5 of 2; ii) the introduction of a methoxycarbonylmethyl group at C-6 of the piperidine ring, either through anodic oxidation followed by nucleophilic substitution [11] (route A), or by using the CN(R,S) methodology [12] (route B); iii) the hydroxyethylation of the nitrogen atom of 9, followed by lactonization. [6] Scheme 2. Synthesis of (ϩ)-(2S,6S)-1a and (ϩ)-(2R,6S)-1b; reagents: i. LDA, HMPA, THF, Ϫ78°C; ii.…”