Steroids intermediates

A sequence of standard transformations of the oxo-steroid intermediate (267) then ultimately led to the desired product (268). In our opinion, this sequence could be applied equally well to tlie preparation of 19-d3-testosterone acetate in high isotopic purity by methylating (266) with da-methyl iodide. 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

The furan nucleus has also been employed as a building block in the construction of steroid intermediates (73JCS(P1)2420). 2, 4 -Dimethoxyacetophenone was condensed with furfural to give the furfurylidene product (64) which on acid hydrolysis furnished the heptanoic acid (65). Cyclization of (65) proceeded smoothly in alkali to yield the cyclopen-tenone acid (66) which was converted to the cyclopentanaphthalene (67) on boiling in acetic anhydride (Scheme 16). 

The desired diol can be isolated after hydrolysis. Woodward noted, that his modification of the Prevost reaction offers the opposite facial selectivity as compared to oxidations with 0s04 in the hydroxylation of synthetic steroid intermediates. Here, the steric approach factors first direct the stereochemistry of the iodination, which is followed by hydroxylation from the opposite face, whereas 0s04 leads to the isomeric cw-diol by direct attack from the most accessible face. 

The conjugate addition with a naphthyl group affords the addition product. Methylation, reductive cleavage of the sulfinyl group, and alkylation give the optically pure steroid intermediate (eq 3). ... 

Synthesis from Steroidal and Alkaloidal Intermediates Steroidal intermediates have been employed in the synthesis of certain alkaloids such as dihydroconessine (58)(ref.55), one of the 3-aminoconanine bases, from the bile acid compound 3-B-acetoxybisnorcholenic acid, a substance obtained from appropriately-protected coprostanol by oxidation and two Barbier-Wieland degradations. The method consisted in converting the carboxyl into a formylamino group, the acetoxy into a tosylate which was then substituted by a dimethylamino group, reduction of the formylamino to methylamino and formation of the five-membered ring E by... 

Woodward, R. B., Brutcher, F. V., Jr. Cis hydroxylation of a synthetic steroid intermediate with iodine, silver acetate, and wet acetic acid. J. 

Transformation of lanosterol to cholesterol (Figure 19-16) is a complex, multistep process catalyzed by enzymes of the endoplasmic reticulum (microsomes). A cytosolic sterol carrier protein is also required and presumably functions as a carrier of steroid intermediates from one catalytic site to the next but may also affect activity of the enzymes. The reactions consist of removal of the three methyl groups attached to C4 and C14, migration of the double bond from the 8,9- to the 5,6-position, and saturation of the double bond in the side chain. Conversion of lanosterol to cholesterol occurs principally via 7-dehydrocholesterol and to a minor extent via desmosterol. 

Several of these optically active compounds were used for the synthesis of natural products. Thus (R)- and (S)-dimethyloctalones 5 lead, respectively, to natural and ent-geosmin,f9 while another natural product was obtained from (S.S)-dimethyloctalone 6, itself a natural compound.fs Compounds 7 and 8 were used to synthesize a ring C aromatic steroidal and a key [ABC] steroid intermediate,22 respectively. 

The new enone 15 condenses in turn in a second Michael addition with the keto-ester 16 under equilibrating conditions to form, presumably, intermediates like 17a and/or 17b. This gum is not isolated but hydrolysed and decarboxylated to give the steroid intermediate 18. 

Upjohn and Pharmacia have used the steroidal intermediate, bisnoraldehyde, to make progesterone and corticosteroids for many years. Recently, they developed a new oxidation process for conversion of the primary alcohol to bisnoraldehyde (4.63). This uses sodium hypochlorite bleach with 4-hydroxy-2,2,6,6-tetramethyl-l-piperidiny-loxy radical in a two-phase system.299... 

Procedures for preparing new steroid intermediates and ergot alkaloids have been further developed. A new method of bioconversion was elaborated for the degradation of sterine side-chains, which allowed selective degradation of the side-chain without damaging the sterane skeleton. 

The reaction mechanism for 7a-dehydroxylation of bile acids was first investigated by Samuelsson [55] using doubly labeled cholic acid fed to conventional rats. The reaction was reported to occur by a diaxial trans elimination of water (6)8-H, 7a-OH) yielding a postulated A -steroid intermediate followed by trans hydrogenation at the 6a and 7 positions generating the secondary bile acids (Fig. 2). Studies... 

During the past three years, we have had excellent success in achieving some asymmetric syntheses O). We have focused attention specifically on faithful transfer of chirality from the sulfur atom of some a-carbonyl a,3-ethylenic sulfoxides to the 3-carbon atom during organometalllc 3-addition reactions. This type of high asymmetric induction in forming carbon-carbon bonds has led to successful preparation of several classes of optically active synthetic intermediates such as 3-methylalkanoic acids and 3-methylcycloalkanones. In addition, this asymmetric methodology has been applied successfully to preparation of more complex, enantiomerically pure molecules such as steroids and steroid intermediates. 

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