Cecropia juvenile hormone synthesis

Caryophyllenes, as an example of two naturally occurring isomeric sesquiterpenes containing a medium-sized ring, in which the success of the total syntheses lies in the stereoselective control of a chiral centre, in a common synthetic key intermediate, which governs the configuration (JE or Z) of the double bonds present in each one of the two isomers. In this context, a brief reference to Cecropia Juvenile Hormone synthesis by the Syntex group, as well as to Johnson s cationic cyclisation of unsaturated polyolefins to fused polycyclic compounds, is made. 

Stereospecific Synthesis of Trisubstituted Olefins from Acetylenes or Aldehydes Applications to the Total Synthesis of Cecropia Juvenile Hormones (JH) and Farnesol... 

Epoxyfarnesol was first prepared by van Tamelen, Stomi, Hessler, and Schwartz 4 using essentially this procedure. It is based on the findings of van Tamelen and Curphey5 that N-bromosuccinimide in a polar solvent was a considerably more selective oxidant than others they tried. This method has been applied to produce terminally epoxidized mono-, sesqui-, di-, and triterpene systems for biosynthetic studies and bioorganic synthesis.6 It has also been applied successfully in a simple synthesis of tritium-labeled squalene [2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-, (all-E)-] and squalene-2,3-oxide [Oxirane, 2,2-dimethyl-3-(3,7,12,16,20-pentamethyl-3,7,ll,-15,19-heneicosapentaenyl)-, (all-E)-],7 and in the synthesis of Cecropia juvenile hormone.8... 

Where would you make the first disconnection to devise a convergent synthesis for (14), whose epoxide is the cecropia juvenile hormone What reaction and what starting materials might you use ... 

The Wharton-Grob fragmentation and the cationic cyclisation of polyolefins. Synthesis o/Cecropia juvenile hormone and d, -progesterone. 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

The thiapyran ring does, like thiophene, provide a heterocyclic system on which one can perform standard sorts of reactions and then through a reductive desulfurization step expose a functionalized carbon chain. Such chemistry was first employed in a very elegant synthesis of the Cecropia juvenile hormones (Scheme 166) (73JA4444). 

Exercise 30-9 The synthesis of Cecropia juvenile hormone outlined below was designed by E. J. Corey and co-workers. Draw in the structure of the product (as i, ii, etc.) at each stage where this has been omitted, and write above the arrows the reagents and conditions necessary to accomplish reactions where these have been omitted. (To save space, the abbreviation R and R are used to designate parts of the structure that do not change in later steps.)... 

Conversion of a terminal alkyne to its alkynylsilane prevents loss of the relatively acidic terminal hydrogen (pKa of ethyne c. 25) during later synthetic steps. For example, the terminal hydrogen of propyne was masked whilst its propargylic anion was used in a synthesis of Cecropia juvenile hormone, a chemical which plays ail important role in insect development (Figure Si5.2). 

In the next examples, formaldehyde makes a primary alcohol from two deprotonated alkynes. The second reaction here (for which we have shown organolithium formation, reaction, and quench simply as a series of three consecutive reagents) forms one of the last steps of the synthesis of Cecropia juvenile hormone whose structure you met right at the beginning of the chapter. 

Diorganocuprates couple readily with vinylic halides and have been employed in the synthesis of some natural products, e.g., fulvoplumieren and Cecropia juvenile hormone (26, 27, 62, 63). Copper-halogen exchange can occur simultaneously 174, 309). Successful coupling reactions of organocopper compounds with vinylic halides are listed in Table VIII. 

Still etal have reported a highly stereoselective synthesis of the alcohol ( 4) which has been previously converted into the Cis Cecropia Juvenile Hormone (Scheme 3). The key step in this synthesis involves the recently described [2,3] sigmatropic rearrangement of the dilithio dianion derived from (13). Full details of the previously reported Ci and Cig Cecropia Juvenile Hormone syntheses have been published."... 

The same general scheme provided a synthesis of the C15 Cecropia juvenile hormone. 

It has also been used in a convenient synthesis of bishomofamesol (3), a in one synthesis of the Cis-Cecropia juvenile hormone (4)/... 

This strategy has been applied to the synthesis of the Cis Cecropia juvenile hormone (JH) (163 Scheme 13) using the ketal (160) rather than an alkoxy butadiene. Surprisingly, an a,p-unsaturated ester is obtained as an -3 1 mixture from which the undesired ( )-isomer can be separated by fractional distillation. The iterated allylic alcohol (163) is transformed into its isomeric allylic cohol which is subsequently reduced to an alkene and epoxidized to realize the target (163). The scheme also lends itself to... 

The method has been used in biogenetic-type synthesis of di- and triterpenes it has also been used in the synthesis of Cecropia juvenile hormone. ... 

Reactions between a-thioallyllithiums and allyl halides, which usually proceed predominantly via OL-CL (head-to-head) coupling, have proved to be valuable in synthesis.They have been used successfully for example in the synthesis of 1,5-dienes such as squalene, (/ )-(-(-)-10,11-epoxyfamesol, (/ )-(+)- and (S)-(-)-2,3-oxidosqualene and mokupalide, dendrolasin, cembra-nolides, methyl ceriferate and Cecropia juvenile hormone (Scheme 25 and Scheme 26). ... 

Two original syntheses of Cis Cecropia juvenile hormones are depicted in Scheme 26, - both of which use the strategy presented above. The second synthesis is particularly ingenious since the dihydro-... 

Faulkner and Petersen1 also used the Claisen rearrangement for a synthesis of the optically active forms of Cecropia juvenile hormone (8). The stereoselectivity in this case was not so high as in the synthesis of squalene. 

The method was developed particularly for one step in the synthesis of the Cl8-Cecropia juvenile hormone.43 Thus the alcohol (10) was transformed into the methyl ester (11) in 70% yield. 

An iterative in situ transvinylation-Claisen rearrangement was employed for the synthesis of the Cl8 Cecropia juvenile hormone (Jll). In this case, the stereoselectivity of the first-step rearrangement is unexpectedly low [(EjZ) 87 13]. The isomers can be separated by fractional distillation using a spinning band column. The second rearrangement proceeds with 100% E selectivity. 

This study of the stereoselective synthesis of trisubstituted double bonds was undertaken in connection with synthesis of substances of the Cn-Cecropia juvenile hormone type, such as (5), the Cj-homologue of the natural hormone. The first step involved stereospecific synthesis of the E-acetal ester (4, 99.5% E-isomer) by addition of an organocopper reagent to an acetylenic ester. The product was converted by several steps into (5). 

In certain cases, the displacement reaction proceeds via an Sn2 mechanism. Synthesis of Cecropia juvenile hormone (LIX) from transjrans-farncsol has been achieved by this method (van Tamelen and McCormick, 1970). 

The [2,3] sigmatropic rearrangement of the alkoxyorganolithium reagent derived from (119) constitutes a key step in the >95% stereoselective synthesis of (120), a precursor of the Cig Cecropia juvenile hormone. The synthesis of the precursor (118) has also been improved as outlined in Scheme 23. ... 

Stereo-controlled methods for synthesis of (386) and (387) are illustrated (Scheme 21) (386) has been converted into (388), a key intermediate in the synthesis of Cjg Cecropia juvenile hormone. The thiopyran (389) has been used for a shrewd stereospecific synthesis of racemic Cecropia juvenile hormone (390) following the route indicated (Scheme 22). ... 

Synthesis.—Much effort has been expended recently in devising new methods for stereospecific syntheses of substituted olefins and, in particular, their application to the synthesis of biologically important terpenoids. Studies of Ci7 and Ci8 Cecropia juvenile hormone necessitated a stereospecific synthesis of the heptenol (241), which was prepared as shown. Conversion of the... 

Chapter 11 Olefin Synthesis and Cecropia Juvenile Hormone... 

---