Lactones steroids

Dehydrogenation of S-lactones. Steroidal <5-lactones are dehydrogenated by hcn/enescleninic anhydride in good yield, but y-lactones are essentially unreactive.3 I1, x a in pie ... 

In this brief article, I will focus on the ways we have learned from the chemistry of the life process itself. However, I must first call attention to another part of natural chemistry that has an effect on chemical thinking the field called the Chemistry of Natural Products. Chemists have explored nature and have discovered several special types of chemicals sugars, fats, ter-penes, alkaloids, acetogenins, amino acids, heterocyclic coloring matters, macrocyclic lactones, steroid hormones, and so on. (2). These compounds have been produced by living organisms and they are secreted by or isolated from them. This field is concerned with the substances of nature and the biochemical processes by which they are formed. 

A D-ring lactone steroid, A -testololactone (101), is used in the clinic in the treatment of breast cancer [217] and has also been described as a competitive inhibitor for AR [216]. More recent findings have shown (101) to be a suicide inhibitor which inactivates AR in a NADPH-dependent process with an apparent of 350 nM [218]. However, testolactone itself which lacks the A -double bond is a simple competitive inhibitor [218]. This finding is consistent with the data described for the A -derivatives of androstenedione (see p. 273) and seems to reinforce the suggestion that the irreversible action of this type of derivative is due to activation of the A -double bond or to the lack of an extractable IjS-hydrogen. 

Achari B, Bandyopadhyay S, Saha C R, Pakrashi S C 1983 A phenanthroid lactone, steroid and lignans from Aristolochia indica. Heterocycles 20 771-774... 

Iguchi, K., Iwashima, M., and Watanabe, K (1995b) Stoloniolide I and 11, new marine lactonic steroids with an unprecedented 1,10-secoergostane skeleton from the Okinawan soft coral, Clavularia viridis. Chem. Lett., 1109-1110. 

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],... 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

Spironolactone is the most clinically usehil steroidal aldosterone antagonist, and unlike GR antagonists, this compound is utilized much more frequendy than aldosterone agonists. Interfering with reabsorption and secretion in the late distal segment, this compound is predominantiy used with other diuretics. Canrenone, an olefinic metaboHte of spironolactone, and potassium canrenoate, in which the C-17 lactone has been hydrolyzed open, are also potent mineralocorticoid antagonists. 

In steroids of the 5 -H series, however, the situation with respect to C-19 substitution changes (Figure 12-3). Displacement is now favored from 11 and abstraction from 6j5. Accordingly, 11, 19-ethers and 6/ , 19-hemiacetals or lactones are the main products. 

No systematic study of the minimal required amount of lead tetraacetate has been made. In cases where the product of the hypoiodite reaction is an iodo ether (20-hydroxy steroids) the reaction can be interrupted at the iodohydrin stage by reducing the amount of iodine to about 0.5 mole. For the oxidation of iodo ethers to lactones, chromium trioxide-sulfuric acid in acetone has been used. Silver chromate is often added to the reaction mixture but comparable yields are obtained without the addition of silver salt. 

Hydroxy steroids afford 18,20-lactones in 48-74 % yield in the presence of other substituents such as acetates, ketals and saturated and unsaturated ketones. However only a 24% yield is reported in the presence of an 11-ketone . Tertiary 20-hydroxy-20-methyl pregnanes still give 18,20-lactones in 45% yield although a competitive cleavage of the 17,20-bond is also observed. 

Chemical synthesis of vitanolides, steroid 8-lactones 97KPS178. 

Synthesis of polyoxysteroids of Achlya (steroid y- and 8-lactones) 98KPS3. 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

THF/liq. NH3, followed sequentially by oxidation and base-induced double bond isomerization, provides butenolide 33, a compound that possesses the lactone system of the steroidal cardiac aglycones. 

Na+/K+-ATPase. Figure 2 Specific Inhibitors of Na+/K+-ATPase. (a) Endogenous cardiac glycosides identified in mammals. Substances with a 5-membered lactone at position C17 of the steroid moiety are referred to as cardenolides, those with a 6-membered lactone as bufadienolides. (b) Palytoxin (C P NsO ) produced by corals of the genus Palythoa. 

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

The y-lactone ring of the steroid skeleton forms an intermediate cardenohde anion in alkaline medium that nucleophilically adds to the 3,5-dinitrobenzoic acid in the position ortho to the two nitro groups. A mesomerically stabilized red-violet anion is produced (Meisenheimer complex). 

Because the reactive intermediate 1277 and methanesulfenyl chloride 1278 are electrophiles, they can react with olefins [72-75]. Thus d -steroids give rise to 6-)9-methylmercapto-zl" -steroids [74]. trans-6-Phenylcyclohex-3-ene-3-carboxyUc add 1291 reacts with DMSO/MesSiBr 16 to form, via 1292, the lactone 1293 in 87% yield, whereas attempted bromolactonization of 1291 affords only 59% 1294 [75] (Scheme 8.29). 

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