Periplanone B, synthesis

Based on the successful series of transformations summarized in Scheme 1, Schreiber and Santini developed an efficient and elegant synthesis of periplanone B (1),8 the potent sex pheromone of the American cockroach, Periplaneta americana. This work constitutes the second total synthesis of periplanone B, and it was reported approximately five years after the landmark periplanone B synthesis by W.C. Still9 (see Chapter 13). As in the first synthesis by Still, Schreiber s approach to periplanone B takes full advantage of the facility with which functionalized 5-cyclodecen-l-one systems can be constructed via anionic oxy-Cope rearrangements of readily available divinylcyclohexanols.5 7 In addition, both syntheses of periplanone B masterfully use the conformational preferences of cyclo-decanoid frameworks to control the stereo- and regiochemical course of reactions carried out on the periphery of such ring systems.10... 

In 1952, it was reported that a constituent of excretions from female American cockroaches of the species Periplaneta ameri-cana is an extraordinarily potent sex pheromone.1 Early attempts to isolate and characterize the active compounds were hampered because individual cockroaches store only minute amounts of the pheromone ( 1 pg), and a full 25 years elapsed before Persoons et al. reported the isolation of two extremely active compounds, periplanones A and B.2 The latter substance is present in larger relative measure and its germacranoid structure (1, without stereochemistry) was tentatively assigned on the basis of spectroscopic data. Thus, in 1976, the constitution of periplanone B was known but there remained a stereochemical problem of a rather serious nature. Roughly three years intervened between the report of the gross structure of periplanone B and the first total synthesis of this substance by W. C. Still at Columbia.3... 

In this beautiful synthesis of periplanone B, Still demonstrated a classical aspect and use of total synthesis - the unambiguous establishment of the structure of a natural product. More impressively, he demonstrated the usefulness of the anionic oxy-Cope rearrangement in the construction of ten-membered rings and the feasibility of exploiting conformational preferences of these medium-sized rings to direct the stereochemical course of chemical reactions on such templates. 

The 1,5 relationship between the olefin and keto groups in 13 satisfies the structural prerequisite for the oxy-Cope transform,11 and, like the first synthesis of periplanone B by Still,9 Schreiber s strategy recognizes that an anionic oxy-Cope rearrangement could provide a powerful and direct method for the assembly of cyclode-cenone 13. On the basis of the model study described previously, it was projected that deprotonation of the free hydroxyl group in 14... 

One of the most remarkable recent achievements was the synthesis of periplanone-(B) (63) the sex excitant of the American cockroach. At the time the synthesis... 

In another approach to periplanone B by Cauwberghs and De Clercq, an intramolecular Diels-Alder reaction of furan-allene 122 afforded a mixture of two exo adducts 123 and 124 and an endo adduct (not pictured) in 90% yield and a 5 4 1 ratio (Scheme 19.23) [28], Refluxing the mixture in mesitylene (N2, 164 °C) afforded a 2 1 equilibrium mixture of 123-124 through a cydoreversion process. The Diels-Alder adduct 123 was converted to 125 via a series of synthetic manipulations, which constituted a formal total synthesis of periplanone B (126). 

Still, W. C. (1979). ( )-Periplanone-B. Total synthesis and structure of the sex excitant pheromone of the American cockroach. Journal of the American Chemical Society 101 2493-2495. 

Identification of cockroach sex pheromones. More than two decades have passed since the identification and chemical synthesis of periplanone-B in... 

This sequence was used later in the synthesis of Mori s intermediate in the course of the total synthesis of (—)-Periplanone-B (Scheme 13).93... 

We finish this pair of chapters about pericyclic reactions with a synthesis whose simplicity is outclassed only by its elegance. Periplanone B is a remarkable bis-epoxide that functions as the sex pheromone of the American cockroach. Insect sex pheromones often have economic importance because they can form the key to remarkable effective traps for insect pests. 

The determination of the absolute configuration of peripla-none-B by American scientists in cooperation with Persoons (38) and the confirmation of the structure by the elegant synthesis of Still at the Columbia University (39) followed in 1979. The planar and stereostructure of periplanone-B are shown in Figure 11. 

The p-stannyl silylenol ether is a useful protection device for a, -enones, as the ethers are relatively unreacdve towards most nucleophiles and are reconverted to the enone on mild oxidation. This form of protection was developed and employed in the acquisition of a crucial disubsdtuted cyclohex-2-enone (7) required in the synthesis of ( )-periplanone-B, a sex pheromone of the American cockroach. Similarly, this sequence was successful in effecting (Z, ) to ( , ) isomerization of isoacorageimacrone (8) to acoragermacrone (9), when other methods e.g. photoisomeiization) failed (Scheme 10). ... 

Selective introduction of an epoxide function was achieved during the total synthesis of racemic periplanone B. Dienone 30 [EEO = OCH(OEt)CH3] yielded monoepoxide 31 as the sole product when epoxidized with zm-butyl hydroperoxide/Triton B/tetrahydrofuran, while compound 32 gave a 4 1 mixture of diastereomers 33 and 34 87. Epoxidation of 35 gave single epoxide 3688, as well as the racemic version of the transformation 17— -18 (p 4667)89. 

From 1976 to 1978, tremendous efforts were spent on the isolation of a major component (in a pure form) of the sex pheromone of the female cockroach, Periplaneta americana. The potency of the compound isolated, periplanone B, was truly amazing (threshold limits of 10 pg). It was considered to be a promising agent to control this pest. However, only trace amounts were isolated from natural sources (a total of 0.2 mg isolated from 75 000 specimens). Even the use of modern methods of instrumental analysis did not lead to the elucidation of its complete structure. With the help of these methods it was possible only to ascertain the basic structural features, as shown in formula 59a (Scheme 1.16). The problem of its stereochemistry remained unanswered. This most difficult part of the problem was finally solved only after a total synthesis of three of four possible geometrical isomers of periplanone Comparison of the spectral parameters of synthetic samples with those of the natural periplanone B determined the stereochemistry as shown in structure 59b. A minor component of the same pheromone, periplanone A, was available in even... 

Figure 24.4 illustrates how a directed aldol reaction was used in the synthesis of periplanone B, the. sex pheromone of the female American cockroach. 

Periplanone B is an extremely active compound produced in small amounts by the female American cockroach. Its structure was determined using 200 pg of periplanone B from more than 75,000 female cockroaches. This structure was confirmed by synthesis in the laboratory in 1979. 

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