Cedranes

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

Toyota, Ihara and coworkers [178] used a combination of a Wacker- and a Heck-type transformation to construct the cedrane skeleton. Thus, reaction of 6/1-374 using 10mol% Pd(OAc)2 under an atmosphere of 02 led to the domino product 6/1-375 in 30% yield. In addition, 58% of the mono-cyclized compound 6/1-376 was obtained (Scheme 6/1.94). 

Oxidation of cedranes and their derivatives by RuCyaq. Na(104)/CCl4-CH3CN (anhydrous RUCI3 does not work) was studied thus epicedrane was hydroxylated regioselectively with retention of configuration to 8a-cedranol (Fig. 4.4), and other oxyfunctionalisations of non-activated C-H bonds in cedranes were similarly accomplished (Table 4.1, cf. mech. Ch. 1) [69]. 

This reaction in the presence of base was applied to a tandem cyclization. When bis-alkynyl silyl enol ether 93a was irradiated in toluene in the presence of 10 mol % W(CO)6 and DABCO with 1 equiv of H2O, the expected tricyclic ketone 94a was obtained in 80% yield. The five-membered substrate 93b also gave the corresponding tricyclic ketone 94b having the basic carbon skeleton of the cedranes. Thus we can prepare synthetically useful tricyclic compounds utilizing this W (CO)5(L)-catalyzed tandem cyclization in the presence of DABCO [25c] (Scheme 5.29). 

An alternative synthesis of pyrimidine boronic acids, which avoids lithiation chemistry altogether, has been developed <2001SL266>. Thus, reaction of 2,4-dimethoxy-5-iodopyrimidine 352 with cedrane-8,9-diolborane 351 using catalytic amounts of Pd(PPh3)4 and Cul gave the intermediate boronate 353 which could be converted to the free boronic acid 354 in 83% yield by transesterification with diethanolamine, followed by treatment with acid (Scheme 3) <2001SL266>. 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

Sesquiterp. cedrane and duprezianane (Juniperus spp., Cupressaceae, Gymn. Barrero 2000) rearr. dumortanes (Dumortiera spp., Marchantiales liverworth, Bryoph. from Argentina Asakawa 1995) pseudoeuaiane Ambrosia maritima L., Compositae, Ang. from Meditrarranean and Africa AY). 

Barrero, A.F. Quilra del Moral, J. Lara, A. (2000) Sesquiterpenes frcHn Jmiperus thurifera L. Staeochemistry in unusual cedrane and duprezianane saies. Tetrahedron, 56, 3717-23. 

The CD spectra of six derivatives (60-65) of cedran-10-one devoid of a C(8)-C(i3) oxide bridge exhibit negative Cotton effects near 290 nm in accordance with the octant rule and a chair conformation of the six-membered ring151. The corresponding ketones with oxide bridge show a preference for a boat-like conformation and exhibit positive n —> jr Cotton effects152. 

Schmidt, T.J., Muller, E. and Fronczek, F.R. (2001) New allo-cedrane type sesquiterpene hemiketals and further sesquiterpene lactones from fruits of lllicium floridanum. Journal of Natural Products 64(4), 411-414. 

Biosynthetic considerations and the discovery of their co-occurrence with a-cedrene (42) and (+)-zizaene (43) have led to the reformulation of various cedrane derivatives (44 R = Me, CH2OH, CHO, or COzH) found in vetiver oil 76 it is believed that these sesquiterpenoids are formed from the common precursor (45). The metabolites of cedrol found in the urine of rabbits are mainly glucuronides of hydroxylated cedrol derivatives 77 presumably formation of the glucuronide of the tertiary alcohol itself is difficult because of steric hindrance. 

Few synthetically useful examples of the oxidation of ethers by oxygen or ozone have been publish-ed.7 96 Q0 In 1978, Ourisson and coworkers reported that ozonization of the natural product cedrane oxide (43) on silica gel at -78 °C led to the formation of the corresponding lactone (44) in 30% yield (equation 32).A small amount of the tertiary alcohol (45) was also produced. Later, in the course of a chiral total synthesis of compactin, Hirama examined the ozonolysis of the alkene (46 equation 33). ° Under carefully controlled conditions, selective ozonolysis of the double bond could be achieved in 88% yield. However, when excess ozone was employed, significant amounts of the benzoate (47) were obtained, even at -78 C. In subsequent studies, benzyl ethers of primary and secondary alcohols,and carbohydrates were oxidized to the corresponding benzoates in excellent yields. Surprisingly, no further synthetic rqrplications of this reaction have been reported. 

A number of model esters related to lac resin have been prepared. These esters have the basic cedrane skeleton (149) or the C-2 epimeric structure. In an approach to the synthesis of cedrene (152), the intramolecular photocycloaddition of the dienone (150) was carried out at low temperature. A major tricyclic compound (151) was obtained and its structure was verified by X-ray analysis of its anisylidene derivative. Further work is required to bring about the rearrangement of a derivative of (151) to give cedrene. Further details on the hydroxylation (with O3) and chlorination (with PhICl2) of cedrol, patchoulol, and their derivatives have been presented. The results of this study are in keeping with those obtained previously. 

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