Cedrene, natural product

Professor Yates research, reported in over 200 papers, covered a remarkably wide range. He established the structures of complex natural products, such as mangostin, shellolic acid, haplophytine, and the fecapentaenes. He was successful in synthesizing such complex natural products as gambogic acid, various bridged-ring steroids, and cedrene. 

Chappell, D. and Russell, A.T. (2006) From a-cedrene to crinipellin B and onward 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis. Organic tg Biomolecular Chemistry, 4 (24), 4409-4430. 

The presence of a quaternary carbon atom is frequently encountered in sesquiterpene natural products and it often creates a synthetic challenge when two or more quaternary carbon atoms are present contiguously. The synthetic strategies for the construction of quaternary carbon centers involve sigmatropic rearrangements/ intramolecular cycloaddition/ and the reaction of tertiary carbon nucleophiles with a carbon electrophile. Recently, radical cyclization strategies turned out to be very effective for this purpose. For example, Srikrishna utilized the radical cyclization reaction to prepare tricyclo[6.2.1.0 - ]undecane system, which is present in several sesquiterpenes such as zizaenes and prelacinanes, and Chen demonstrated that a tandem radical cyclization approach is an efficient method for constructing the two quaternary carbon centers in the cedrene skeleton. ... 

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

Yamamura has extensively explored the intramolecular [5 - - 2]-cycloaddition mode. This chemistry bears a remarkable similarity to the so-called arene olefin meta-photocycloaddition [64] reaction (e.g., 267 to 268) that has frequently been used in the synthesis of complex bioactive natural products. While different intermediates are involved, the photo-and electrochemical reactions provide access to many of the same basic ring systems. This is nicely demonstrated by comparing key steps and the outcome of an electrochemical approach to the total synthesis of pentalene (53) [65] and a photochemical pathway that ultimately led to cedrene (compare equations 48 and 49). 

This arene-alkene intramolecular meta photocycloaddition was shown to provide the basis for an effective and general approach to polyquinane natural products, such as (+ )-cedrene or ( + )-isocomene. ... 

Chappell, D., Russell, A. T., From a Cedrene to Crinipellin B and Onward 25 Years of the Alkene Arene m Photocycloaddition Reaction in Natural Product Synthesis, Org. Biomol. Chem. 2006, 4, 4409 4430. 

Intramolecular alkylative dearomatization offers a convenient means of constructing spirocyclo-hexadienone ring systems (Scheme 15.1). This reaction has been utilized in a number of total syntheses targeting construction of terpenoid ring systems found in natural products such as cedrene, hinesol, kaurene, p-vetivone, and isolongifolene [5], Subsequently, alkylative dearomatizations have been employed as key steps in approaches toward more complex natural products such as inter alia duocarmycin SA [6], cortistatin A [7], and platensimycin (Scheme 15.2) [8], This last example is notable as it illustrates the ability to employ silyl-protected phenols as masked phenolate anions in high-yielding alkylations. 

When cedrene was oxidised with permanganate, there were chiefly formed products of an acid nature, from which a cedrene keto acid, CjjHj Oa, was isolated, which boiled at 215° to 222° (11 mm. press.). Its semicarbazone melts at 245° and its oxime at 60°. 

The major components of the Cedrus wood oils are cedrol, cedrene and thujopsene, and a number of perfume ingredients are made from these. The most important is acetylated cedarwood. This product is used because it possesses a much stronger cedarwood odour than the natural oil and is available under various trade names such as Lixetone and Vertofix . The acetylation can be carried out using acetyl chloride in the presence of a Lewis acid or by using a Bronsted acid system such as polyphos-phoric acid/acetic anhydride or sulfuric acid/acetic anhydride. The cedrol dehydrates into cedrene under the reaction conditions and so the major component in the product is acetylcedrene. However, the main contributor to the odour of the complex reaction product mixture is the ketone derived from acetylation of thujopsene (Daniker et al., 1972). These reactions are shown in Figure 4.36. 

Tomita and Hirose have reported that the reaction of P-acoradiene (226) with formic acid affords, after saponification, the newly discovered natural sesquiterpene allocedrol (227-OH) (297, 298), along with several other products. The structure of allocedrol is enantiomeric to that obtained by hydration of the carbonium ion intermediate (220) depicted in the zizaene biogenesis. This cyclization is presumably less efficient than the a-acoradiene- cedrene cyclization (213- 214) since ring... 

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