Cholesta-3,5-dien-7-one

The 3,6-cyclo-A-nor-3,5-secoandrostanes (354) were synthesized through reduction of the enol lactones (355) (see ref. 67). The syntheses of 5,7/3-cyclo-B-homo-5/3- and 6/S,7a/S-cyclo-B-homo-5a-cholest-2-enes and derivatives of these were reported.Notably, reaction of the 6j8,7a/3-cyclo-B-homo-compound (356) with HOBr and with peracid gave, in each case, a single product resulting from exclusive -face attack.Methylenation of cholesta-4,6-dien-3-one with dimethyloxosulphonium methylide gave 6/8,7aj8-cyclo-B-homocholest-4-en-3-one and the 6a,7a-epimer. ... 

Kandutsch (142) has also suggested the alternate pathway of biosv nthesis of cholestanol from 7-dehydrocholesterol. Although unable to show the conversion of 7-dehydrocholes-terol to the 3-keto derivatives, he has demonstrated the conversion of cholesta-4,7-dien-3-one and cholesta-4,6-dien-3-one to 4 -cholestenone with the microsomal fraction of mouse liver homogenates. 

Kandutsch, a. a. Metabolism of cholesta-4,7-diene-3-one and cholesta-4,6-dien-3-one by mouse liver microsomes. J. Lipid Res. 4, 179 (1963). 

Irradiation of the 5,7-diene gave the previtamin, which was isomerized and saponified to give la-hydroxy-vitamin D3. For the last synthesis of la-hydroxy-7-dehydrocholesterol recorded here, cholesta-l,4,6-triene-3-one was again used as starting steroid.122 Deconjugation of this trienone with strong base followed by immediate reduction with calcium borohydride led to the unstable 3/3-hydroxycholesta-l,5,7-triene which, without isolation, was converted into the 1,4-addition product (265) upon reaction with 4-phenyl-l,2,4-triazoline-3,5-dione. 

A shorter but less selective route to la-hydroxycholesterol has been described by Kaneko (90). Cholesta-l,4-dien-3-one (90) was deconjugated to its -isomer and then reduced with borohydride to give 3P-hydroxy-cholesta-1,5-diene (91). Selective hydroboration followed by alkaline peroxide treatment afforded a 30% yield of a separable 1 1 mixture of la- and 2a-hydroxycholesterol (89) and (93). If the acetate (92) was hydrated by an oxymercuration-demercuration procedure, a mixture of the 2 3-hydroxycholesterol (94) (14%) and la-hydroxycholesterol (89) (26%) was isolated after saponification (118). When starting with the readily available cholesta-l,4,6-trien-3-one, the deconjugation and reduction afforded 3P-hydroxycholesta-l,5,7-triene (95) (59). The 5,7-diene system was then protected as its 4-phenyl-l,2,4-triazoline-3,5-dione (PTD) adduct (96). Treatment of (96) with m-chloroperbenzoic acid gave a 5 3 mixture of the lp,2p- and la,2a-epoxides (98). More recently, Whalley and his co-workers have found that if the dimethyl-t-... 

Figure 26.4. Fucosterol and other structurally related sterols isolated from seaweeds. (A) Fucosterol (B) 24 -hydroperoxy-24-vinyl cholesterol (C) 29-hydroperoxystigmasta-5,24(28)-dien-3 3-ol (D) 24-ethylcholesta-4,24(28)-dien-3-one (E) 24 -hydroperoxy-24-ethylcholesta-4,28(29)-dien-3-one (F) 24-ethylcholesta-4,24(28)-dien-3,6-one (G) 24 -hydroperoxy-24-ethylcholesta-4,28(29)-dien-3,6-dione (H) 24 -hydroperoxy-6(3-hydroxy-24-ethylcholesta-4,28(29)-dien-3-one and (I) 6(3-hydroxy-24-ethyl-cholesta-4,24(28)-dien-3-one. For details readers may refer to Sheu et al. (1999). 

Cholesta-1,3-diene, -3,5-diene, and -4,6-diene react with PhI(OAc)2-Me3SiN3 to give the la-azido-2-en-4-one, 6/3-azido-4-en-3-one, and 4/3-azido-5-en-7-one, respectively.114... 

The acid-catalysed decomposition of the adducts (291) and (292 R = 0) derived from the parent steroidal 5,7-dienes furnishes a novel route to 4,4-dimethylcholesta-5,7,14(15)-trien-3-one (90%) and cholesta-4,6,8( 14)-trien-3-one respectively.165 It has also been noted that reaction of the adduct (292 R = /3-OAc,H) with boron trifluoride etherate gives an oxidative rearrangement to the anthrasteroid (293)... 

The 2-methoxy-4a-methyl-5Q -androst-2-en-l-one system (500), corresponding to the ring a substitution pattern of quassin, has been elaborated from a 5a-androst-l-en-3-one by application of a sequence of familiar transformations.5,6(8-Epoxy-4/3-hydroxy-5/3-cholest-2-en-l-one (501) has been synthesized as a model for rings A and B of withaferin A (502). The synthesis involved multiple steps from cholesta-2,5-dien-l-one related compounds were synthesized from the 2,4-dien-l-one." ... 

Purified cholesterol, all known initial and subsequent oxidation products of cholesterol and some related compounds were tested cholest-5-en-3-one 7a-diol 73-diol 7-keto cholesta-3,5-dien-7-one a-epoxide triol cholest-4-en-3-one 63-hydroperoxycholest-4-en-3-one 63 hydroxycholest-4-en-3-one cholest-4-ene-3,6-dione cholest-5-ene-33,43 diol 5a-cholest-6-ene-33,5a-diol 53 cholestan-33-ol cholesta-1,4-dien-3-one 5a-cholest-7-eii-33 ol cholesta-7,9-dien-33-ol acetate 7,8,9,11-diepoxy-22-isoallospirostan-33 ol acetate cholesteryl acetoace-tate and cholesteryl isoheptylate. Many were carcinogenic when administered subcutaneously into Marsh-Buffalo mice with sesame oil as the vehicle a-epoxide, 63-hydroperoxycholest-4-en-3-one and cholest-4-en-3,6-dione were most potent (34-66% incidence of fibrosarcoma verses 1.4% for vehicle control). All share the property of oxygen linkage at carbon 6. 63-hydroxycholest-... 

C29H48O2S, Cholestan-4-one-3-spiro(2,5-oxathiolane), 33B, 201 C2 9H49CIO2 r 3p-Acetyloxy-14-chloro-5a,14, 17a-cholestane, 41B, 614 C29Hso02r 9, 10a-Cholesta-5,7-diene-3 -ol ethanol solvate, 40B, 503 C30H33BrF403, 3/3-(p-Bromobenzoyloxy)-androst 5-eno-[16a,17-d]-2 ,2 ,3, 3 -tetrafluoro-2, 3 -dihydro-6-methylpyran, 37B, 302 C30H4 2O7 r 6a,7a 22,26 24,25-Triepoxy-5,26-dihydroxy-5a-ergost-2-en-1-one acetate, 42B, 411... 

In enediones in which two carbonyl groups of a diketone are linked by an ethylenic bond tin [174] and chromous chloride [196] reduce only the double bond, and none of the conjugated carbonyl groups. A double bond conjugated with one carbonyl group only is not reduced. Refluxing cholest-4-ene-3,6-dione with chromous chloride in tetrahydrofuran yielded 49% of 5/S-cholestane-3,6-dione, and a similar reduction of cholesta-l,4-diene-3,6-one gave 5)S-cholest-l-ene-3,6-dione [196]. 

Sevanian et al. (1994) applied GLC and LC/TS/MS for the analysis of plasma cholesterol-7-hydroperoxides and 7-ketocholesterol. Analysis of human and rabbit plasma identified the commonly occurring oxidation products, yet dramatic increases in 7-ketocholesterol and cholesterol-5p, 6P-epoxide were observed. The study failed to reveal the presence of choles-terol-7-hydroperoxides, which were either too unstable for isolation, metabolized or further decomposed. The principal ions of cholesterol oxides monitored by LC/TS/MS were m/z 438 (cholestane triol) m/z 401 (cholesterol-7-hydroperoxide) m/z 401 (7-ketocholesterol) m/z 367 (7a-hydroxycholesterol) m/z 399 (cholesta-3,5-dien-7-one) and m/z 385 (choles-terol-5a,6a-epoxide). The major ions were supported by minor ions consistent with the steroid structure. Kamido et al. (1992a, b) synthesized the cholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as stable secondary oxidation products of cholesteryl arachidonate and linoleate, respectively. These compounds were identified as the 3,5-dinitrophenylhydrazone (DNPH) derivatives by reversed-phase LC/NICI/MS. These standards were used to identify cholesteryl and 7-ketocholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as major components of the cholesteryl ester core aldehydes generated by copper-catalysed peroxidation of low-density lipoprotein (LDL). In addition to 9-oxoalkanoate (major product), minor amounts of the 8, 9, 10, 11 and 12 oxo-alkanoates were also identified among the peroxidation products of cholesteryl linoleate. Peroxidation of cholesteryl arachidonate yielded the 4, 6, 7, 8, 9 and 10 oxo-alkanoates of cholesterol as minor products. The oxysterols resulting from the peroxidation of the steroid ring were mainly 7-keto, 7a-hydroxy and 7P-... 

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