Steroids dimerization

A rather different synthetic method has been developed by Bonar-Law, which involves the synthesis of porphyrins in aqueous micelles derived from sodium dodecylsulfate. This is most appropriate for construction of porphyrins having particular hydrophobic multipoint recognition sites, such as those involving steroid dimers or trans-disubstituted tetraarylporphyrins. ... 

Scheme 4. First preparation of a pyrazine linked steroid dimer.

Subsequent to the isolation of the cephalostatins, there was renewed interest in such steroid dimers. An improved procedure for the preparation of 4 was reported16 by the Fuchs group (Scheme 5), in which the intermediate a-amino ketone was produced in higher yield by the sequence of bromination with phenyltrimethylammonium bromide, displacement by azide to give a-azido ketone 5, and hydrogenation (an identical route was independently developed17 in the Heathcock group). 

The Fusetani group has reported [1] the structures of 13 new ritterazines. Some chemical transformations of ritterazine B and their effect on antitumor activity are also described. The Fuchs group has published [2] a full paper on the total synthesis of cephalostatin 1. They have also prepared two hybrid dimers. The dimer containing the ritterazine G right half coupled to the cephalostatin 1 right half has similar activity to cephalostatin 1. A review has appeared [3] on steroid dimers and oligomers. 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Introduction of Nitrogen into a Terpenoid Skeleton. The acetate-derived fragments (35) mevalonic acid (30), which yields isopentenyl pyrophosphate (31) and its isomer, 3,3-dimethyl ally pyrophosphate (32) a dimeric C -fragment, geranyl pyrophosphate (33), which gives rise to the iridoid loganin (34) and the trimer famesyl pyrophosphate (35), which is also considered the precursor to C q steroids, have already been mentioned (see Table 3... 

Whereas dimerization of two famesyl pyrophosphates (35) generates squalene (114) on the path to steroids (89), the addition of one more C unit, as isopentenyl pyrophosphate (31) or its isomer, 3,3-dimethyl ally pyrophosphate (32), to the C compound famesyl pyrophosphate produces the C2Q diterpene precursor geranylgeranyl pyrophosphate [6699-20-3] (122). 

The reactions of A -steroids with nitrosyl fluoride parallel those of their A -isomers. Thus, 17 -acetoxyandrost-4-ene (37) is converted to the nitrimine (38), in 67 % yield and thence to the 4-ketone (39), which can be dehydrofluorinated to the A -4-ketone (40) with lithium bromide in di-methylformamide. In the corresponding 19-nor series the nitroso dimer is also formed. 

Steroids are heavily modified triterpenoids that are biosynthesized in living organisms from farnesyl diphosphate (Cl5) by a reductive dimerization to the acyclic hydrocarbon squalene (C30), which is converted into lanosterol (Figure 27.12). Further rearrangements and degradations then take place to yield various steroids. The conversion of squalene to lanosterol is among the most... 

With two y,8 double bonds, two a,/3 double bonds, and the possibilities of cis and trans ring fusions with syn and anti configurations, 20 isomeric dimers are possible. Surprisingly, only one product is formed in a head-to-tail fashion. The sole product of the irradiation of the 3,5-diene-7-ketosteroid (76), however, is the head-to-head dimer. The specificity and mode of addition arise presumably through the effect of the specific environment of the chromaphore. The dimerization of (75) is believed to involve the addition of the a,fi double bond of a photoexcited molecule to the less hindered y,8 double bond of a ground state molecule. The photocondensation of (76) with cyclopentene, in which steric hindrance should not be a controlling factor, was found to yield a cyclobutane product involving the a,/ bond of the steroid in contrast to dimerization across the y,8 bond. 

A remaining class of dimerizations is represented by the reactions shown in Eqs. 36—39. These are singlet state reactions, and they are all characterized by stereospecificity and regiospecificity. Production of the trans isomer from the steroidal dienone in Eq. 39 is anomalous and poses a... 

The answer is a. (Hardman, p 1302.) Cyclophosphamide, an alkylating agent, reacts with purine and pyrimidine bases of DNA to form bridges and dimers. These products interfere with DNA replication. 5-FU, methotrexate, and 6-thioguanine are anti metabolites, and the steroid prednisone has some tumor-suppressive effects. 

Fawell SE, Lees JA, White R, Parker MG (1990) Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell 60 953... 

From activated isoprene, the metabolic pathway leads via dimerization to activated geraniol (1 = 2) and then to activated farnesol = 3). At this point, the pathway divides into two. Further extension of farnesol leads to chains with increasing numbers of isoprene units—e.g., phytol (1 = 4), dolichol (1 = 14-24), and rubber = 700-5000). The other pathway involves a head-to-head linkage between two farnesol residues, giving rise to squalene (1 = 6), which, in turn, is converted to cholesterol (1 = 6) and the other steroids. 

Reduction of steroid enones like cholestenone 26, with a rigid ring conformation, leads to head-to-head pinacol dimers because of steric hindrance at the alternative dimerization site, and reaction occurs tlnough the a-face of the radical intermediate [101, 102]. The a-face is opposite to the angular methyl substituent... 

When intermediate 274 reacted with ketones 133 (from D-glucose) or 270 (from D-fructose), mixed steroid-sugar compounds 278 and 279 were, respectively, obtained in low yields (10-16%). In addition, the use of protected estrone 280 (precursor of the epoxide 272) as electrophile allows the preparation of the dimeric steroid 281 in 26% yield. The low yields obtained for compounds 278, 279 and 281 are due to extensive decomposition during their column chromatographic purification. 

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