Farnesyl bromide

C2]-Squalene, 80, has been produced71 in the reaction sequence shown in equation 31 which involves alkylation of 3-13C-ethyl acetoacetate with geranyl bromide, followed by hydrolysis, decarboxylation and treatment with triethyl phosphonoacetate and then reduction of the ester 82 with LiAlHr, bromination with CBr4/PPh3 and coupling the farnesyl bromide with Cul/Li-pyrrolidine. Epoxidation of 80 has been effected by... 

Alternatively to using prelipidated building blocks palmitoylation on resin is possible with the hydrazine linker. In Scheme 27 the synthesis route for the palmitoylated and farnesylated N-Ras peptide 78 is shown. Here the initial loading of trityl-protected cysteine to the hydrazine linker was mediated by A,A-diisopropylcarbodiimide (DIG) and HOBt. After Fmoc removal the proline was coupled using HBTU and HOBt. The trityl-protected dipeptide 75 was subsequently S-deprotected using TFA with triethylsilane (TES) as a scavenger. Farnesylation of the free thiol was achieved with an excess of farnesyl bromide. 

Lipo-amino acid derivatives are readily obtained in good yields by direct alkylation of amino acids esters with the related alkyl halides, e.g. farnesyl bromide, under careful control of the reaction conditions to avoid exhaustive alkylation of the amino group. 128 Alternatively, peptoid chemistry is applied for N-alkylation of glycine ester via reaction of alkyl amines, e.g. hexadecylamine, with ethyl bromoacetate. 36,98 ... 

On treating the anion generated from 2-farnesylthiothiazoline (603) with farnesyl bromide a 44% yield of the squalene derivative (605) was produced. Desulfurization of this intermediate with Raney nickel afforded squalene in 80% yield (Scheme 133). 

In view of the synthetic applications, among carbanions stabilized by only one divalent sulfur atom, allylic thiocarbanions proved to be particularly valuable, as shown with Biellmann coupling of allylic groups, applied to an elegant synthesis of squalene from farnesyl bromide [301]. In this synthesis, the retention of the allylic double bond position and stereochemistry in both the metallation-alkylation and the desulfurization steps are noteworthy. However, the results are not always as clear-cut, and... 

The complex formed on addition of cuprous iodide to a solution of a lithium dialkylamide in ether or tetrahydrofuran is effective in the reductive coupling of allylic halides to give 1,5-dienes with preservation of stereochemistry. This method has been used5 for the stereospecific synthesis of all-trans-squalene and (E,Z,Z,E) squalene from (E,E)- and (Z,JE)-farnesyl bromides, respectively. In an attempted synthesis of (3S)-squalene-2,3-epoxide, 4-[(4R)-2,2,5,5-tetramethyl-l,3-dioxolan-4-yl]butan-2-one (1) and the phosphonium iodide (2) were prepared.6 Unfortu-... 

The best results are obtained with the use of alkali metal hydrides (NaH, KH) in THF, DME, or DMF. The reaction works well in THF or DME with activated halides such as ethyl bromoac-etate, ten-butyl bromoacetate, - ethyl 2-bromobutyratc, ethyl T-broniobulyrale.- (iodom-ethyl)trimethylstannane, " (iodomethyl)trimethylsilane, benzoyl bromide,- benzyl bro-mide, - farnesyl bromide,- " alkyl 4-bromocrotonates, l-(bromomethyl)naphtalene,- andN-bromomethylphthalimide but gives poor results with primary alkyl halides.- Primary and secondary alkyl halides, bromides and iodides (Scheme 8.16), react satisfactorily in dMF or DMSO, although bulky electrophiles give poor results. In DMSO the expected product is frequently contaminated by the dialkylation product. ... 

Puupehenone (62), an antibacterial component of a Hawaiian marine sponge (unknown genus), has been synthesized from farnesyl bromide (56) and the lithium salt of sesamol (57) cf. Scheme 7). 

By the reaction of farnesyl bromide with excess orcinol in dioxane containing silver oxide followed by preparative chromatography a 15 % yield of grifolin was obtained containing only a small proportion of the isomer neogrifolin (ref. 23). 

C-Alkylation. Grifolin (2) has been synthesized in 15% yield by the reaction of orcinol (1, excess) with farnesyl bromide in dry dioxane containing silver oxide. Some of the 4-farnesyl isomer is formed as well. The reaction of orcinol... 

A new alkylation reaction which involves 2-alkenylthiothiazoline lithium derivatives has been applied to the synthesis of squalene. 2-Farnesylthiothi-azoline (1) was converted into its lithium salt (2) and alkylated with farnesyl bromide to form the squalene derivative (3). Desulphurization with Raney Nickel afforded squalene in 80"o yield. 

Coupling of (E,E)-farnesyl bromide with famesylbarium provides all (E)-squalene (79% yield). 

In this synthesis farnesyl bromide (25) was converted with 2-nitropropane and KOH into farnesal (27). Horner-Emmons reaction with the C -phosphonate 28 gave the ester 29 which was reduced with LiAlH4 to the alcohol 30 (32% yield referred to 25) and transformed, with phosphorus tribromide and triphenylphosphine, to the C2o-phosphonium salt 31 (Scheme 7). 

The boviquinones-3 and -4 have been synthesised in moderate yields from 2,5-dihydroxy-l,4-benzoquinone and the corresponding allylic bromide in the presence of a tertiary amine (Scheme 40) (389). It is interesting that the success of these reactions was crucially dependent on the direct use of farnesyl bromide and of geranylgeranyl bromide without special purification. The preparation and properties of the chromenols and chromanols of boviquinone-4 have been reported (71). 

Epichlorohydrin. l-Chloro-2,3-epoxypropane, 856, 978, 984 2-Ethylhydroquinone dimethylether. 2-Ethyl-l,4-dimethoxybenzene, 875 4-Ethylpyrogallol. 4-Ethyl-l,2,3-benzenetriol, 834 2-Ethylresorcinol. 2-Ethyl-l,3-benzenediol, 824 4-Ethylresorcinol. 4-Ethyl-l,3-benzenediol, 825 4-Ethylresorcinol diacetate. 4-Elhyl-l,3-benzenediol diacetate, 825 Farnesyl bromide. 3,7,ll-trimethyl-2,6,10-dodecatrienyl bromide, 1081,... 

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