A Short Stereoselective Synthesis of Cecropia Juvenile Hormone

Abstract

Abstract. A very short synthesis of the racemic cecropia hormone has been realized, utilizing a Claisen reaction. Methyl 6-hydroxy-3-methyl-7-methylene-2-trans-nonenoate, on treatment with the dimethyl ketal of 3-chloro-3-methyl-2-pentanone and a catalytic amount of 2,4-dinitrophenol, is transformed directly into methyl 11-chloro-3, 11-dimethyl-7-ethyl-10-oxo-2-trans, 6-trans-tridecadienoate. Selective reduction gives a mixture of diastereoisomeric chlorohydrins separable by chromatography. The predominant threo-chlorohydrin is transformed into the juvenile hormone. R=CH3 We wish to report a very short, stereoselective synthesis6 of the racemic cecropia hormone 1, which for the first time allows easy access to both the natural trans, trans, cis hormone 1 and its all-trans isomer in pure form.Previously, the allylic alcohol 3 has been shown2 to react with the allylic ketal 4, involving a stereospecific Claisen rearrangement, to produce the unsaturated ketone 5. Although this compound contains the complete skeleton of 1, five steps were required to transform ketone 5 into the racemic juvenile

Simultaneous Preparation of Both Enantiomers of Juvenile Hormones Labeled at C-10 with Tritium at High Specific Activity

“…1. Use of an organocuprate addition to methyl or ethyl 2-butynoate for preparation of 3 or its homologous ethyl ester gave better control of regiospecificity of the 2,3-double bond vs use of a Claisen rearrangement with methyl 2-hydroxy-3-methyl-3-butenoate as reported by Loew et al (8). Similarly, use of a polymeric copper-lithium complex in place of a Grignard reagent for the addition to aldehyde 5 gave the nonenoate 6a in better yield.…”

“…The stereoselective synthesis of JH I developed by Loew et al (8) was modified using the methods of Anderson et al (12) for JH 0 synthesis to improve the yield, reproducibility, and purity. This improved synthesis is outlined in Fig.…”

“…The crude chloroketone product from the Claisen was separated on preparative (1.5 mm) 20 ϫ 20 cm TLC silica gel plates (developed in 10% ethyl acetate/hexane). The chloroketone was further purified with preparative normal phase HPLC using isocratic conditions (4% ether/hexane) as described above with monitoring at both 254 and 220 nm to give 1.6 g (4.87 mmol, 65% yield) 7a; NMR (CDCl 3 ) ␦ 1.6 (s, 3, C-11, CH 3 (8). To a small glass test tube suspended in ice water was added a magnetic stir bar and 1.2 mg of JH I methyl ester chloroketone (methyl (2E,6E)-11-chloro-3,11-dimethyl-7-ethyl-10-oxo-2,6-tridecadienoate) in 20 l of isopropanol.…”

A Stereoselective Synthesis ofdl-C17-CecropiaJuvenile Hormone

“…Its reduction with sodium borahydride in isopropanol-ethanol yielded the 3.58 (3H, s), 5.00 (2H, br). 5.54 (lH, br.…”

“…C1o-unit (IV) bp 120~ 121 'C (0.1 mmHg); o (CCI,, 100 MHz)1.60 (3H, s),1.64 (3H, s),3.83 (2H, s),4.51 (lH, br. s),5.25 (2H, br.…”