Total Synthesis Of Steroids Research Articles

Terminal olefins synthesized using cheap butadiene

Due to their high profile biological activity, the steroids are among the most important secondary metabolites. A review of literature on the total synthesis of steroids starting from BISTRO (1,8-bis(trimethylsilyl)-2,6-octadiene) is presented.

ChemInform Abstract: Stereoselective Enzymatic Reduction of Ethyl Secodione: Preparation of a Key Intermediate for the Total Synthesis of Steroids.

Ethyl secodione (1) has been enantioselectively reduced by using different biocatalysts for the preparation of ethyl secol (13R, 17S)-2a. The recombinant ketoreductase KRED1-Pglu converted the substrate with the highest reaction rate and stereoselectivity (ee > 98 %), whereas whole cells of Pichia minuta CBS 1708 showed the highest productivity. Stereoselective reduction of 1 provides the key chiral precursor for the synthesis of a number of hormonal contraceptives (i.e., desogestrel, norgestrel, gestodene).

Stereoselective Enzymatic Reduction of Ethyl Secodione: Preparation of a Key Intermediate for the Total Synthesis of Steroids

AbstractEthyl secodione (1) has been enantioselectively reduced by using different biocatalysts for the preparation of ethyl secol (13R, 17S)‐2a. The recombinant ketoreductase KRED1‐Pglu converted the substrate with the highest reaction rate and stereoselectivity (ee > 98 %), whereas whole cells of Pichia minuta CBS 1708 showed the highest productivity. Stereoselective reduction of 1 provides the key chiral precursor for the synthesis of a number of hormonal contraceptives (i.e., desogestrel, norgestrel, gestodene).

ChemInform Abstract: Total Synthesis of Steroids and Heterosteroids from BISTRO

AbstractReview: 134 refs.

Synthesis of 6‐Oxaestra‐1,3,5(10),8,14‐pentaenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of 6-oxaestra-1,3,5(10),8,14-pentaenes

The Wendler version of the Torgov-Ananchenko scheme of total steroid synthesis was shown to be applicable to the preparation of 6-oxaestra-1,3,5(10),8,14-pentaenes. Conditions for cyclodehydration of secosteroids thus obtained were found, which ensured isolation of the target compounds in a high yield without using chromatographic purification methods.

Neurosteroid analogues. 6. The synthesis and GABAA receptor pharmacology of enantiomers of dehydroepiandrosterone sulfate, pregnenolone sulfate, and (3alpha,5beta)-3-hydroxypregnan-20-one sulfate.

The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3alpha,5beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABAA receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers. The IC50s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 microM, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC50s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 microM, respectively. The IC50s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 microM, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABAA receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site for these steroids does not exist on GABAA receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

Effective Ring Formations and Natural Product Syntheses

Simple and effective synthetic methods of polycylic ring systems in intramolecular reactions are presented. The first example is Diels-Alder reaction, which has been applied to total synthesis of steroids and terpenes. The intramolecular double Michael reaction is the second case, whose mechanism and application to natural product synthesis are also discussed. In addition, some related reactions of the latter are described.

ChemInform Abstract: New Aspects of the Catalytic Hydrogenation of 2,3,5,6,7,7a‐Hexahydro‐1. beta.‐hydroxy‐7aβ‐methyl‐5‐oxo‐1H‐indene‐4‐propionic Acid, an Important Intermediate in the Total Synthesis of Steroids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Intramolecular, Reductive Coupling of Bis‐α,β‐unsaturated Ketones.

AbstractThe reduction‐rearrangement procedure of the vinylogous β‐diketone (I), tricyclic intermediate in the Wilds total steroid synthesis, gives the tetracyclic diketone (II), which isomerizes to the spiro diketone (III).

Intramolecular, Reductive Coupling of Bis‐α,β‐unsaturated Ketones

AbstractThe reduction‐rearrangement chemistry of two rigidly held doubly vinylogous β‐diketones has been investigated. One hydrophenanthrene dienedione was a tricyclic intermediate in the Wilds total steroid synthesis and the other was prepared from the Wieland‐Miescher ketone. Lithium‐ammonia reduction yielded a cyclopropanedione and a cyclopropanoketol, respectively. Treatment of these compounds with acid furnished cyclopropane‐cleaved ketoenones.

A new synthesis of (±) and (+)-2, 6, 7, 7a-tetrahydro-1β-hydroxy-4-formyl-7aβ-methylindenes

A new method for the preparation of the synthon (±)-2,6,7,7a-tetrahydro-1β-hydroxy-4-formyl-7aβ-methylindene (1,a) for the total synthesis of steroids in both (±) and (+) forms, starting from the known β-ketoester, (±)-methyl 1β-t-butoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-keto-4-indancarboxylate (2,a) has been described. An alternative route to (1,a) has been investigated. Although the compound, (±)-1β-hydroxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-keto-4-methoxymethylindan (2,b) could not be prepared, interesting pathways leading to two unexpected products, (±)-5,6,7,7a-tetrahydro-4,7a-dimethyl-5H-indene-1,5-dione and (±)-2,6-diketo-3-methyltricyclo-(5,2,1,0)decan-8-ol (3 and 4), were encountered during an attempted annelation reaction of the ketone, N-diethylamino-5-methoxypentan-3-one (6), with 2-methylcyclopentan-1,3-dione (5). Trapping of the intermediate, (±)-3a,4,5,6,7,7a-hexahydro-3a-hydroxy-4-methylene-7a-methylindene-1,5-dione (7), through the formation of the adduct, (±)-3a,4,5,6,7,7a-hexahydro-3a-hydroxy-4-(1′, 3′-diketo-2′-methylcyclopentano-2′-methylene)-7a-methylindene-1,5-dione (8), established the mechanism of the formation of the products (3 and 4).

ChemInform Abstract: Biomimetic Total Synthesis of Steroids. Part 10. Synthesis of 7‐(Methoxymethyl)‐ and 7‐(Phenylmethoxymethyl)‐19‐norsteroids.

AbstractCationic cyclization of the alcohols (VIII), prepared from the diester (I), yields the title compounds (IX) and (X) as major products.

Biomimetic total synthesis of steroids X. Synthesis of 7‐(methoxymethyl)‐ and 7‐(phenylmethoxymethyl)‐19‐norsteroids

AbstractCationic cyclization of 2‐[6‐(m‐methoxyphenyl)‐5‐(methoxymethyl)‐(E)‐3‐hexenyl]‐3‐ methyl‐2‐cyclopentenol 23a and of the phenylmethoxymethyl analogue 23b has been studied. Although oxygen participation with the cyclization by the ether group is possible, and was observed, cyclization to steroids remains the major pathway.The decreased stereoselectivity, when compared with the cyclization of the 7‐methyl analogues, may be due to the occurrence of boat‐like transition states.

Control of steroid synthesis in adrenal fasciculata cells.

The control of steroid synthesis in adrenal fasciculata cells is considered in terms of two types of control by ACTH: control of cholesterol availability to inner mitochondrial cytochrome P-450scc. This process controls total steroid synthesis and is rapidly activated by ACTH. The several steps in cholesterol transfer are examined. partitioning of metabolism by means of competition between enzymes for limiting amounts of steroid intermediates. Changes in such competition determine the ratio of steroid products from the adrenal cells. Such changes typically are a slower response to ACTH. A critical aspect of such competition is the modulation of multiple activity P-450 cytochromes: P-450(17 alpha) (17 alpha-hydroxylation and 17,20 lyase) and P-450(11 beta) (11 beta- and 18-oxidases). Factors such as substrate binding, electron transfer steps and lipid environment are considered in addition to new enzyme synthesis. The ACTH stimulation of steroid synthesis in bovine adrenal cell primary cultures is examined as a model for both types of regulation.

Biomimetic total synthesis of steroids, IX. Stereospecific synthesis of C‐homo‐19‐norsteroids

AbstractCationic cyclization of 2‐[7‐(3‐methoxyphenyl)‐(E)‐4‐heptenyl]‐3‐methyl‐2‐cyclopentenol (1c) produced 3‐methoxy‐17‐methyl‐C‐homo‐1,3,5(10),13(17)‐gonatetraene (3c) and its 1‐methoxy isomer 2c. Epoxidation of 3c with tert‐butyl hydroperoxide in the presence of molybdenum hexacarbonyl produced the corresponding 13α, 17α‐epoxide 14 as the major product, which, in three steps, was converted into C‐homo‐1,3,5(10)‐estratriene‐3,17β‐diol (18).

Total synthesis of steroids. Part 2. Preparation of C-10 methylated steroids. Regio- and stereocontrol in a diene addition to methyl Z-2-methyl-4-oxo-2-pentenoate

A twelve-step total synthesis of 14-epi-androsta-4,9(11),15-triene-3,17-dione from methyl vinyl ketone, 2-methylcyclo-hexane-1,3-dione, acetylene, and methyl Z-2-methyl-4-oxo-2-pentenoate is described. Crucial steps include a stereo- and regio-selective diene addition, an efficient formation of ring D by C-acylation of an acetyl group, and a selective bromine substitution at C-15 in a 15,17-dione intermediate. The stereo- and regioselectivity of the diene addition is generalized for certain other bifunctional aliphatic dienophiles.

Cobalt-mediated total synthesis of steroids. The A .fwdarw. BCD approach by enediyne cyclization

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCobalt-mediated total synthesis of steroids. The A .fwdarw. BCD approach by enediyne cyclizationEthan D. Sternberg and K. Peter C. VollhardtCite this: J. Org. Chem. 1984, 49, 9, 1574–1583Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://doi.org/10.1021/jo00183a018RIGHTS & PERMISSIONSArticle Views501Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

Additions and Corrections - Cobalt-Mediated [2 + 2 + 2] Cycloadditions En Route to Natural Products: A Novel Total Synthesis of Steroids via the One-Step Construction of the B,C,D Framework from an A-Ring Precursor.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdditions and Corrections - Cobalt-Mediated [2 + 2 + 2] Cycloadditions En Route to Natural Products: A Novel Total Synthesis of Steroids via the One-Step Construction of the B,C,D Framework from an A-Ring Precursor.Ethan Sternberg and K. Peter VolhardtCite this: J. Org. Chem. 1983, 48, 26, 5413Publication Date (Print):December 1, 1983Publication History Published online16 October 2003Published inissue 1 December 1983https://doi.org/10.1021/jo00174a603RIGHTS & PERMISSIONSArticle Views38Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (149 KB) Get e-Alerts Get e-Alerts

Camphorae: chiral intermediates for the enantiospecific total synthesis of steroids. 1

On prepare une benzo [e] indenone, intermediaire de synthese de la cortisone, a partir du borneol (−)