Steroid analogues

A domino RCM of an ene-yne was also used by Granja and coworkers [250] for their synthesis of the B-bishomo-steroid analogue 6/3-70. Reaction of the substrate 6/3-69 with the ruthenium catalyst 6/3-13 led to 6/3-70 in 48% yield as a 6.5 l-mix-ture of the two C-10-epimers (Scheme 6/3.20). The aim of this study was to prepare haptenes for the production of catalytic monoclonal antibodies that could be used to study the mechanism of the physiologically important transformation of previtamin D3 into vitamin D3 [251]. 

In order to study heterocyclic steroid analogues, such as the 7,11-dithiaazasteroid analogues, Fravolini developed the synthesis of new heterocyclic ring systems tri- and tetracyclic 2,1-benzothiazines <82JHC1045>. Intermediate 137 was prepared from 1-methyl-4-oxo-lH-2, -bcnzothiazinc-4(3f/)-onc 2,2-dioxide 37 and thioglycolic acid and could be converted into 6-methyl-4-oxo-3,4-dihydro-2//,6//-thiopyrano[3,2-c][2,l]benzothiazine 5,5-dioxide 138 by cyclization with polyphosphoric acid. The reaction of 138 with dimethyl... 

On the other hand, in the synthesis of cholesterol (30) by Woodward and CO workers [10] the less stable fran -configuration between rings C and D is attained through a homosteroid (29). i.e. a steroid analogue in which the C/D indane system is substituted by a decalin in which the rran -configuration is the thermodynamically favoured (Scheme 8.7). The conversion of the six-membered ring into one of five members is carried out at a later stage, under conditions that do not affect the preformed tran -junction. 

While these steroids can be extracted directly from human tissue, in most instances they can also be synthesized chemically. Direct chemical synthesis methodology has also facilitated the development of synthetic steroid analogues. Many such analogues exhibit therapeutic advantages over the native hormone, e.g. they may be more potent, be absorbed intact from the digestive tract, or exhibit a longer duration of action in the body. The majority of sex steroid hormones now used clinically are chemically synthesized. 

Fluasterone is a stable adrenocortical steroid analogue ofprasterone (dehydroepi-androsterone (DHEA)) fluorinated at C-16a (Figure 8.85). It is currently being developed (Phase II) for the treatment of metabolic syndrome (i.e., insulin resistance). Electrophilic fluoration with NF type reagent is well adapted for the synthesis of such as a-fluoroketone (95%, a /i 95 5). ... 

Other fluoroaromatic compounds such as fluorobenzene, trifluorotoluene and their derivatives may be elaborated to more complex aromatic compounds by directed metallation reactions (in itself, the subject of another large review [322-324]). Wakselman and co-workers described the conversion of 3-tri-fluoromethylphenol into 2-(trifluoromethyl)-l,3-cyclopentadienone, an intermediate they used to synthesise angularly trifluoromethylated steroid analogues [325]. The reaction, which involved an interesting ring contraction reaction, occurred with rather low efficiency (Eq. 122) [326]. 

As an extension of this work, Mattay et al. have used this methodology for the construction of unnatural steroid analogues [41]. The polycyclic framework was build-up via a cascade cyclization of the silyl enol ether 32 using DCA as sensitizer (Sch. 19). The two major products 33 were formed with remarkable high trans, //-stereoselectivity. 

Molecules of widely different structures may produce such aggregation behavior. Hence compounds as diverse as anthracene alkyl ethers [69a], cyclic depsipeptides [69b], gluconamides [69c], steroid analogues [69d], and polar compounds containing long apolar moieties [69e], all show gelation abilities in different solvents. 

In 1953, Fried and Sabo announced the synthesis of the highly potent steroid analogue fludrocortisone (9-fluoro-hydrocortisone), formally accenting the beginning of the analogue era [10-13]. 

The androgen testosterone is made in the testis and directs developmental maturation of male sex characteristics and normal function of male sex organs. Anabolic—androgenic steroid analogue drugs have been developed for increasing muscle mass. 

A further paper elaborates upon the internal aldol condensation of an 8,9-seco-8,9,11-trione to give so-called linear steroid analogues. ... 

Pipecuronium bromide is a bisquaternary steroid analogue of pancuronium. In vitro pipecuronium reversibly inhibits both human red cell acetylcholinesterase and human plasma cholinesterase to an extent that might have clinical implications (1). Its potency is similar to that of pancuronium and its onset and duration are also approximately the same. Accumulation can occur (2), and maintenance doses should be one-quarter to one-sixth of the initial dose to achieve a similar effect, depending on the anesthetic technique used. 

In addition to lesiolaclone, two other steroid analogues have been used. A well-studied steroid analogue is 4-hydroxy-... 

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