Famesol derivatives

The tandem oxacydization of a triepoxide was also explored. On treatment with BF3 Et20, the famesol-derived triepoxide 84, with a tert-butylcarbonate as the nucleophilic terminating functional group, afforded the tricyclic bis-oxepane 85 as the major product (52%, Scheme 8.21). The tetraepoxide derived from geranylger-aniol was similarly converted into the corresponding tetracyclic structure [39a]. 

CycHzation offar esol. This complex (1) is superior to other Hg(Il) reagents for rcgioselective cyclizatibn of various famesol derivatives. The product (3) obtained in this... 

Onocerane triterpenes. This reagent was used in the first synthesis of the unsym-metrieal a, -onoceradiencdione (8) for cyclization of two famesol derivatives, (2) and (6), to A/B-rra/i.r, 9/IO-c(.s decalin systems. 

A problem in the use of dimethylallyl pyrophosphate (3) is its instability. In a study of this problem the half-life of this substance was examined over a range of pH values and temperatures. Both cis- and trans-prenyl pyrophosphates (4 n = 0, 1, or 2) occur in Pinus radiata. Their biosynthesis from [2- C,3R,4K- H]-mevalonic acid proceeded with retention of tritium whereas with [2- C,3K,4S- HJmevalonic acid tritium was lost [except in the case of isopentenyl pyrophosphate (4 n = 0)]. The authors suggest that since they could not detect an isomerase, there may be a cis- and a trans-prenyl transferase both of which eliminate the label derived from [4S- H]mevalonic acid. However, compart-mentalization may have resulted in the isomerase not being available to the administered monoterpenoids, although it may act on geranyl pyrophosphate formed in situ. The absence of 6-cis-famesol derivatives tends to support this idea. Further work on this system again produced no evidence for isomerization or metabolism of [l- H]nerol pyrophosphate to 2-rrans-6-c(s-farnesyl pyrophosphate. 

Juvenile hormone, larval hormone, stalus-quo hormone insect hormone responsible for the control of molting. The first J.h. to be isolated and structurally elucidated was obtained from the abdomens of the male silk worm moth (Hyalophora cecropia) in 200 ig quantities. Homologs of this compound were discovered later, and other J.h. were postulated. Juva-bione (see) and famesol derivatives are among the... 

Corey and Yamamoto 233) used the P-oxido synthesis 2341 of trisubstituted olefins for the preparation of the acyclic sesquiterpene famesol 433. In this preparation the isoheptenylphosphonium salt 430 is converted into the hydroxyfamesol derivative 432 by reaction with the tetrahydropyranyl ether — protected hydroxy aldehyde 431 and formaldehyde 205. 432 is converted into famesol 433 via several steps. Other reactions of432 likewise proceeding via several steps lead to 434 which is a positional isomer of a C17-juvenile hormone 233) (Scheme 75). 

The synthesis of the limondd azadiradione, utiiizing a Hg° cyclization-oxidative demercuration sequence with an enol phosphate derived from trans,trans-famesol has been reported. Azadiradione, a te-tracarbocyclic memter of the iimonoid group isoiated from the neem tree, Azadirachta indica, has been converted to other tetracyclic limonoids, and is thus a key intermediate. The sequence is shown in Scheme 33. 

Another forefront technique to improve the function of the stratum corneum and enhance barrier repair in dry skin is the use of epidermal differentiation. A number of hormone receptors for epidermal differentiation have been identified. This family of receptors includes retinoic acid receptors, the steroid receptors, the thyroid receptors, the Vitamin D receptors, the peroxisome proliferator-activated receptors, the farnesol-activated receptors, and the liver-activated receptors. It is reported that these transcription factors bind their respective ligands and regulate many of the aspects of cellular proliferation and differentiation. Examples of ligands for the last three transcription factors are fatty acids for the peroxisome proliferator-activated receptor, famesol for the farnesol-activated receptor, and hydroxylated cholesterol derivatives for the liver-activated receptor. The stimulation of epidermal differentiation stimulated the synthesis of involucrin, filaggrin, and the enzymes of the ceramide synthesis pathway (74). 

Based on the structural diversity of the many congeners originating from Laurencia, the elucidation of a bios5mthetic mechanism for the likely development of these metabolites is of much interest. The isolation and characterization of monoepoxide 30 (Scheme 1) from Laurencia okamurai [15] has allowed investigators to postulate that this compound (30) may be a common precursor for the biosynthesis of all other secondary metabolites derived from squalene [3]. Its absolute stereochemistry was verified via asymmetric synthesis utilizing a Sharpless asymmetric epoxidation [16] of trans, trara-famesol,... 

Famesol (alcohol from 6 n = 2) is an efficient precursor of ipomeamarone (45). A derivative of the 2-cis-isomer of famesol is, presumably, the immediate precursor of the furan ring of this terpenoid, and the ant metabolite dendrolasin... 

The common names of these intermediates derive from the sources from which they were first isolated. Geraniol, a component of rose oil, has the aroma of geraniums, and famesol is an aromatic compound found in the flowers of the Farnese acacia tree. Many natural... 

In addition to crinitol, two structurally related minor acyclic diterpene alcohols, geranylgeraniol (3) and phytol, were also isolated from the active fraction in S. tortile, although neither of them exhibited any activity up to 800 / g/ml as listed in Table 1. In addition, several derivatives of crinitol as well as its two common natural congeners, famesol... 

Sesquiterpenes (sesquiterpenoids). A structurally highly diverse class of terpenoids with 15 carbon atoms skeleton derived biosynthetically from famesyl pyrophosphate (FPP) ( famesol, isoprene rule, ter-penes). More than 70 different ring systems are formed by enzyme-catalyzed cyclization of the linear parent structure these cyclic structures can be further modified by 1,2- and 1,3-hydride shifts, renewed cycliza-tions, hydroxylations, and other subsequent reactions. S. are widely distributed in plants, fiingi, and animals but are less common in bacteria. Specific biosynthetic routes are often characteristic for certain organisms. Thus, basidiomycetes preferentially use humulene as the basis for the syntheses of protoilludanes, illu-danes, lactaranes, hirsutanes, and related S. skeletons. Individual S. systems are also known for liverworts and marine organisms. In addition, liverworts often contain the optical antipodes of S. known from plants. 

Most acyclic sesquiterpenes are derived from famesol and nerolidol (7) or from the corresponding pyrophosphate esters. Although the number of acyclic sesquiterpenes is relatively small, Z- and -famesol (5 and 6), nerolidol (7), and the corresponding olefins are relatively common in essential oils. The famesenes and a few other compounds, such as 3-sinesal (8), are derived in a straightforward manner, but most acyclic sesquiterpenes are more complex in origin (Fig. 21.4). 

Figure 5.22 shows a tiny fraction of the biosynthetic pathways derived from (Z, )-famesyl pyrophosphate. Direct hydrolysis leads to acyclic sesquiterpenoids such as famesol (111) and nerolidol... 

We present here some significant examples in cyclization using Pd-catalyzed allyla-tion, in carbocycle and macrolide chemistry. Humulene, a fundamental monocyclic sesquiterpene, is derived biologically from famesol by anti-Markownikov cyclization no synthesis of this terpene by such cyclization had been realized before the highly stereoselective synthesis presented by Yamamoto and co-workers. The acyclic sesquiterpene skeleton was constructed starting with geranyl acetate via the ( ,ii)-bromide 316, which... 

Usually, carotenoid is used to indicate C4o-compounds consisting of eight isopentenylpyrophosphate (IPP) units. Some variations in carbon numbers of carotenoids are also observed (Table 106.1). Cao-carotenoids are synthesized by the combination of two famesol instead of the usual geranylgeraniol unit. C45- and Cso-carotenoids are synthesized by the addition of one and two IPP units to C4o-carotenoids, respectively. Unique carotenoid derivatives, such as carotenoid glycoside fatty acid esters and carotenoid sulfates, are also distributed in specific organisms (Table 106.1). 

Two units of isoprene combine to form terpenes, Cjo compounds such as geraniol. Three isoprene units form sesquiterpenes, C15 compounds such as famesol. Diterpenes are C20 compotmds, triterpenes are C30 compounds, and so on. Myriad terpenoid compounds are known, and most can be traced to derivatives of isoprene as starting material. Most terpenes follow the isoprene rule, which dictates the head-to-t ul formation described earlier. AH of the terpenes shown in Figure 12.76 do not stricdy follow the pattern, but each has at least one head-to-tail connection. 

Alkynyltriisopropylsilanes. The acidic alkynic H can be protected with TIPS triflate. Silylation of l-Uthiopropyne with 1 equiv of TIPS triflate in ether at —40 to 0 °C gives an 87% yield of 1-TIPS-propyne (eq 4). 1,3-Bis(triisopropylsilyl)propyne, derived from treatment of 1-TIPS-propyne with n-butyllithium in THF at —20 °C for 15 min followed by TIPS triflate at —78 to —40 °C (eq 5), is lithiated with n-BuLi in THF at —20 °C for 15 min and then allowed to react with aldehydes (eq 6). The Ci5-enynes are isolated in high yields. TlPS-propargylmag-nesium bromide together with copper(T) iodide has been used in the displacement of the mesylate derivative of famesol. ... 

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