Improved syntheses of hydroxy acid precursors of macrolide pheromones of cucujid grain beetles

Abstract

Can. J. Chem. 64,1407 (1986. Syntheses of 11-and 12-hydroxy-(2)-3-dodecenic, 11-and 12-hydroxy-(Z,Z)-3,6-dodecadienic, and 13-hydroxy-(Z,Z)-5,8-tetradecadienic acids are reported. These unsaturated hydroxy acids are precursors of male-produced macrolide aggregation pheromones of grain beetles of the genera Cryptolestes and Oryzaephilus. The sequence of reactions for synthesis of the hydroxy-(Z)-3 acids was carboxylation of the dilithium salt of 10-or 11-hydroxy undecyne, deconjugation of the resulting carboxylic acids with NaNHz in THFIliquid ammonia to a mixture of 2,3-allenic and 3-alkynoic acids, and hydrogenation of the mixture with P-2 nickel catalyst. This latter reaction gave only the desired hydroxy-(Z)-3-alkenoic acids. The convergent point in the syntheses of the diunsaturated hydroxy-(Z,Z) acids was the coupling of the dimagnesium salt of 3-butyn-1-01 or 5-hexyn-1-01 to the appropriate functionalized propargylic bromide. The resulting 1 ,Cdiacetylenic alcohols were oxidized with Jones reagent to the corresponding carboxylic acids, which were hydrogenated over P-2 nickel catalyst and deprotected. convergence des synthbses des hydroxy-acides di'insaturks-(Z,Z) est le couplage du sel de dimagnksium du butyne-3 01 ou de I'hexyne-5 01 avec le bromure propargylique fonctionnalisk d'une f a~o n appropriie. On a oxydt les alcools di-acktylkniques-l,4 qui en rksultent avec le rtactif de Jones; on a hydrogknt les acides carboxyliques correspondants sur un catalyseur P-2 de nickel et on les a ensuite dkprotkgt.[Traduit par la revue] Introduction During the past several years, we have reported (1-6) the discovery of seven macrolide aggregation pheromones for five species of grain beetles (Table 1). These well-known cucujids are economically-important pests during grain storage, food processing and distribution, and in households. The beetles infest a wide variety of stored-product commodities such as grain, cereal-based foods, nuts, chocolate, oil seeds and cake, raisins and other dried fruits, and spices.Our initial syntheses (7-9) of these macrolides were long and, in cases, inefficient, but furnished sufficient amounts of the pheromones for laboratory bioassays. In order to supply selected macrolides for laboratory trap tests and limited field trials, we have devised more efficient syntheses of the o and o -1 hydroxy acid precursors of macrolides 1-4 and 6. As in previous approaches, we have utilized functionalized alkynes for carbon-carbon bond formation by coupling with appropriate electrophiles and for conversion into the required Z-olefinic bonds. In this paper, we report new syntheses for the hydroxy acid precursors of macrolides 1 and 6 and improved routes to those of macrolides 2-4.

Synthesis of stable isotope–labeled chloroquine and amodiaquine and their metabolites

“…This compound was prepared following a reported procedure as outlined below: To a stirred solution of 5‐chloro‐2‐pentanone (12.05 g, 100 mmol) in 95% EtOH (100 mL) was added NaBH 4 portionwise at 0°C. The mixture was stirred at 0°C for 30 minutes and allowed to warm to room temperature and stir for 2 hours.…”