Prenylation

The intramolecular insertion of an internal alkyne into an aryl or alkenyl halide 727 generates aryl- or alkenylpalladium as an intermediate, which is trapped with an organozinc or organostannane to give 728. Overall cis addition to the alkyne takes place[595,596]. The reaction of the alkenylstannane 730 with the 2-bromomethylfuran 729 is used for the introduction of a prenyl group[597]. 

Synthesis of P-Methylheptenone from Petrochemical Sources. p-MethyUieptenone (1) is an important intermediate in the total synthesis of terpenes. Continuous hydrochlorination of isoprene [78-79-5] produces prenyl chloride [505-60-6] which then reacts with acetone with a quaternary ammonium catalyst and sodium hydroxide to give P-methyUieptenone (6-methyIhept-5-en-2-one [110-93-0]) (eq. 1) (16—19). 

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Chromone, 2,3-dichloro-7-methoxy-synthesis, 3, 825 Chromone, dihydromass spectra, 2, 23 Chromone, 3,5-dihydroxy-2-methyl-selective methylation, 3, 716 Chromone, 5,7-dihydroxy-2-methyl-prenylation, 3, 716 Chromone, 3,7-dimethoxy-2-methyl-reactions... 

Useful selectivity between allyl and 3-methylbut-2-enyl (prenyl) ethers has been achieved. ... 

Four different types of lipid-anchoring motifs have been found to date. These are amide-linked myristoyl anchors, thioester-linked fatty acyl anchors, thioether-linked prenyl anchors, and amide-linked glycosyl phosphatidylinosi-tol anchors. Each of these anchoring motifs is used by a variety of membrane proteins, but each nonetheless exhibits a characteristic pattern of structural requirements. 

FIGURE 9.19 Proteins containing the C-terminal sequence CAAX can undergo prenylation reactions that place thioether-linked farnesyl or geranylgeranyl groups at the cysteine side chain. Prenylation is accompanied by removal of the AAX peptide and methylation of the carboxyl group of the cysteine residue, which has become the C-terminal residue. 

The farnesylation and subsequent processing of the Ras protein. Following farnesylation by the FTase, the carboxy-terminal VLS peptide is removed by a prenyl protein-specific endoprotease (PPSEP) in the ER, and then a prenylprotein-specific methyltransferase (PPSMT) donates a methyl group from S-adenosylmethionine (SAM) to the carboxy-terminal S-farnesylated cysteine. Einally, palmitates are added to cysteine residues near the C-terminus of the protein. 

Gelb, M. H., 1997. Protein prenylation, et cetera Signal transdnction in two dimensions. Science 275 1750-1751. 

Glomset, J. A., Gelb, M. H., and Farnswordi, C. C., 1990. Prenyl proteins in eukaryotic cells A new type of membrane anchor. Trends in Biochemical Sciences 15 139—142. 

Methylbut-2-enyl (Prenyl) Ester (CH3)2C=CHCH202CR Cleavage... 

The cinnamyl ester can be prepared from an activated carboxylic acid derivative and cinnamyl alcohol or by transesterification with cinnamyl alcohol in the presence of the H-Beta Zeolite (toluene, reflux, 8 h, 59-96% yield). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°, 2-A h KSCN, H2O, 23°, 12-16 h, 90% yield]or by treatment with Sulfated-Sn02, toluene, anisole, reflux. The latter conditions also cleave crotyl and prenyl esters. 

Pd(OAc)2, TPPTS, CH3CN, H2O, Et2NH, 30 min, 89-99% yield. Deprotection can be achieved in the presence of a prenyl or cinnamyl ester, but as the reaction times increase, these esters are also cleaved.Prenyl carbamates and allyl carbonates are cleaved similarly. 

Prenyl amine (66) was long used in the treatment of angina pectoris, in which condition it was believed to act by inhibiting the uptake and storage of catecholamines in heart tissue. Droprenilamine (69), an analogue in which the phenyl ring is reduced, acts as a coronary vasodilator. One of several syntheses involves simple reductive alkylation of 1,1-diphenyl-propylamine (67) with cyclohexyl acetone (68)... 

Several 2-butenylboron reagents have been synthesized by the hydroboration of allenes9 36. Diisopinoeampheyl(3-methyl-2-butenyl)borane is an excellent reagent for the asymmetric iso-prenylation of aldehydes (typically 89 95% ee), and is conveniently synthesized by the hydroboration of 3-methyl-l,2-butadiene using diisopinocampheylborane9. 

Lipidation -acylation TV -myristoylation Myristoy-lation S-prenylation Prenylation Palmitoylation Isoprenylation GPI anchors Glypiation... 

S-prenyl (famesyl) T T T S-Cys Cysteine at/near carboxyl-terminus... 

S-prenylation is the most recent of the four major types of lipid modifications to be described. As with -acylation, S-prenylation is posttranslational. The lipid substrates for these modifications are farnesyl diphosphate and geranylgeranyl diphosphate. The mechanism... 

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