Synthesis of (3S,6RS)- and (3RS,6RS)-Analogs of Component AI of the Aonidiella aurantii Sex Pheromone by Stepwise Alkylation of Acetoacetic Ester

Abstract

O AcO O CO 2 Et AcO X + CO 2 Et O + Br 1 2 3 B A C AcO O CO 2 Et AcO Br [10] AcO CO 2 Et O 3 5 4NaH / C PhH -DMFKey words: acetoacetic ester, 1,5-bifunctional 3-methylpentanes, 3-butenylbromide, sex pheromone of California red scale (Aonidiella aurantii), ethyl ester of 2-acetyl-7-acetoxy-2-(3-butenyl)-5-methylheptanoic acid, synthesis.The natural component AI of the California red scale (Aonidiella aurantii) citrus pest sex pheromone has been identified as (3S)-methyl-(6R)-isopropenyldec-9-en-1-ol acetate (1) [1]. Biological tests showed that the (S)-configuration of asymmetric C-3 is the most important for attractiveness [2]. Known schemes for synthesizing (3S)-1 were developed starting from (S)-citronellol [2-5] and (-)-dihydrocarvone [6]. Furthermore, it has been found [2] that enantiomers, which were prepared previously from (±)-citronellol as a diastereomeric mixture of 1 acetates, do not inhibit the biological activity of AI [2, 3, 7-9].Herein we report synthetic approaches to the acetates of 1 and (3S)-1. Retrosynthesis of 1 showed that keto-precursor 2 could be prepared by decarbethoxylation of α,α′-disubstituted derivative 3 of acetoacetic ester (A), for which, in turn, the substituting agents are conveniently 1,5-bifunctional 3-methylpentanes (B) and a homoallyl bromide (C).Key intermediate 3 for the synthesis of optically inert 1 was prepared by condensation of α-substituted acetoacetic ester 4 [10], the product of monoalkylation of the CH-acid A by 1-acetoxy-5-bromo-3-methylpentane (5) [11], bromide B.