Squalene epoxy

S. are biosynthesized by cyclization of 2,3-epoxy-squalene (see Squalene) in the case of the steroid S., cholesterol is a subsequent intermediate in the biosynthesis of the spirostane skeleton. The stage at which the sugar b omes attached and the mechanism of this attachment are not known. 

Squalene occurs in cod-liver oil and in several vegetable oils, for example those from rape and cotton seed. Red algae Laurencia okamurai produce (+)-l,10-epoxy-squalene. Botryococcane is the parent hydrocarbon of some branched and alkylated triterpenoid polyenes found in the algae Botryococcus braunii and referred to as C3o-C37-botryococcenes, depending on the number of their carbon atoms. 

The enzymatic formation of steroid type materials from the open chain epoxy squalenes (Scheme 10.10) are normally accomplished using extract of mammalian liver cells. Although exciting as a synthesis these preparations can only be achieved on very small (mg scale) substrate conversions. Sonochemistry has afforded an inexpensive and convenient alternative... 

Hexaepoxy squalene, HES (Scheme 70) was used as a multifunctional initiator in the presence of TiCU as a coinitiator, di-f-butylpyridine as a proton trap, and N,N-dimethylacetamide as an electron pair donor in methylcy-clohexane/methyl chloride solvent mixtures at - 80 °C for the synthesis of (PIB-fc-PS)n star-block copolymers [145]. IB was polymerized first followed by the addition of styrene. The efficiency and the functionality of the initiator were greatly influenced by both the HES/IB ratio and the concentration ofTiCL, thus indicating that all epoxy initiation sites were not equivalent for polymerization. Depending on the reaction conditions stars with 3 to 10 arms were synthesized. The molecular weight distribution of the initial PIB stars was fairly narrow (Mw/Mn < 1.2), but it was sufficiently increased after the polymerization of styrene (1.32 < Mw/Mn < 1.88). 

Sodium toluene dispersion of, 55, 65 Sodium p-toluenesulfinate, 57, 103 Spiro[4 n] alkenones, 58, 62 Spiro[cyclopentane-l,l -indene] 55, 94 Squalene, 56, 116 Squalene, 2,3-epoxy, 56, 116 Stannic chloride, 56, 97 Steroids synthesis, 58, 85 E Stilbene, 55, 115,58, 73 z-Stilbene, 58, 133 Styrene, 56, 35,58, 43 Styrene glycol, 55, 116 Styrene glycol dimesylate, 55, 116 Succinic acid, 58, 85 Succinic anhydride, 58, 85 Sucunimide, 56, 50, 58, 126 Succimmide, Vbromo, 55, 28, 56, 49 SULFIDE CONTRACTION, 55, 127 Sulfide, dimethyl-, 56, 37 SULFIDE SYNTHESIS, 58, 143,58, 138 SULFIDE SYNTHESIS ALKYL ARYL SULFIDES, 58, 143 SULFIDE SYNTHFSIS DIALKYL SULFIDES, 58, 143 SULFIDE SYNTHESIS UNSYMMETRI-CAL DIALKYL DISULFIDES, 58, 147 SULFONYL CYANIDES, 57, 88 Sulfur tetrafluoride, 57, 51... 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

Epoxidation of (Z)-2-methyl-2-hepten-l-ol gave epoxy alcohol 61 (80% yield, 89% ee) [2], of (Z)-2-methyl-4-phenyl-2-buten-l-ol gave 62 (90%, 91% ee) 177], and of (2T)-1 -hydroxy squalene gave 63 (93%, 78% ee) [85]. The epoxy alcohol 64 had >95% ee after recrystallization [91], In the epoxidation of (Z)-2-r-butyl-2-buten-l-ol, the allylic alcohol with a C-2 r-butyl group, the epoxy alcohol was obtained in 43% yield and with 60% ee [38], These results lead one to expect that other 2,3Z-disubstituted allylic alcohols will be epoxidized in good yield and with enantioselectivity similar to that observed for the 3Z-monosubstituted allylic alcohols (i.e., 80-95% ee). 

The epoxy alcohol (47) is a squalene oxide analog which has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast The epoxy alcohol (48) provided an optically active intermediate used in the synthesis of 3,6-epoxyauriq>tene and marmine, and epoxy alcdiol (49) served as an intermediate in the synthesis of the antibiotic virantmycin. In the synthesis of the three stilbene... 

An enzyme system from the yeast Saccharomyces cerevisiae is able to incorporate isoprenoid precursors into the C30 phytoene analogue (200) only in the presence of Mn and absence of NADPH. If NAD PH is present and Mn is replaced by Mg, the sterol precursor squalene (201) is produced.The substrate specificity of the chloroplast enzyme violaxanthin deepoxidase has been examined.In addition to the normal substrate violaxanthin [(35,5/ ,65,3 5,5 i ,6 5)- 5,6,5, 6 -diepoxy-5,6,5, 6 -tetrahydro-/3,j8-carotene-3,3-diol, (196)] several all-trans-monoepoxy-carotenoids, such as anthera-xanthin [5,6-epoxy-5,6-dihydro-/3,/3-carotene-3,3 -diol (197)], diadinoxanthin [5,6-epoxy-7, 8 -didehydro-5,6-dihydro-j8, 8-carotene-3,3 -diol (198)], and /3-cryptoxanthin epoxide [5,6-epoxy-5,6-dihydro-/3,/3-caroten-3-ol (199)], all with the 38,5R,6S) configuration, were utilized. Violeoxanthin (9-cis-violaxanthin) and other 9-cis-isomers were not affected. A carrot Daucus carota) tissue culture has been shown to incorporate [ C]acetate into carotenoids. ... 

The synthesis of tricyclic compounds based on the cyclisation of methyl geranyl-geranoate was described eighteen years ago. However, the discovery of expoxy-squalene as an intermediate in steroid biosynthesis, and the corresponding in vitro cyclisation experiments, have re-awoken interest in this area of diterpene synthesis. The structural and stereochemical course of the in vitro cyclisation of the epoxy-trans-olefin (138) has been studied. Two A/B-trans-fused tricyclic compounds (139) and (140) have been isolated. The levantenolides (142) and (143) have been obtained by two closely related routes. In the first, the butenolide (141), derived from monocyclofamesyl bromide, afforded the a- and P levantenolides (142) and (143) on cyclisation with stannic chloride. In the second, the corresponding acyclic butenolide derived from famesyl bromide was cyclised. 

The enzyme involved is squalene 2,3-oxide cycloartenol cyclase and the substrate is the S enantiomer. The reaction is initiated by H" " attack on the oxygen of the epoxy group of the substrate held in the chair, boat, chair, boat unfolded conforma-... 

The triterpenoids constitute a large diverse group of active natural products derived from squalene. In excess of 4000 triterpenoids have been isolated so far and more than 40 skeletal types have been identified. In general, triterpenes arise by cyclisation of squalene or the 3S isomer of 2,3-epoxy-2,3 -dihydrosqualene. Cyclisation of this isomer leads to 3p-hydroxytriterpenoids which, by oxidation and reduction, can be transformed into 3a-hydroxyterpenoids. 

Optically active epoxy-terpenes have aroused considerable interest in recent years because of their intermediacy in biosynthetic pathways. Several reports on the syntheses of chiral terpenes have appeared, " among which are the syntheses of / -( + )- and S-(-)-squalene-2,3-oxide from L-glutamic acid (Scheme 1). 

ToF-SIMS, and also in some cases XPS, has been applied to a range of polymer problems such as adhesion studies of elastomers based on brominated poly(isobutylene-co-4-methylstyrene) and diene elastomers [229], PVC [230], epoxy resin aluminium [231,232], glass rubber [233], squalene brass [234], and sealants [235]. 

FIGURE 8.8 A biological epoxi-dation reaction of the alkene squalene, a step in steroid biosynthesis. The reaction is effected by a flavin hydroperoxide formed by reaction of O2 with the coenzyme reduced flavin adenine dinucleotide, FADH2. 

Figure 20.21 shows more clearly the cydisation process in which squalene is firstly oxidised via squalene epoxi-dase to form 2,3-squalene epoxide. This then cyclises to produce the basic steroid nucleus, resulting in the formation of lanosterol. This is why all steroids have an oxygen atom at the 3 position. 

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