The ADRENAL HORMONES AND RELATED COMPOUNDS. I. A “DIRECT” SYNTHESIS OF HYDROCORTISONE ACETATE AND CORTISONE ACETATE FROM 11α-Hydroxyprogesterone

Hogg, John A.; Beal, P. F.; Nathan, Alan H.; Lincoln, F. H.; Schneider, William P.; Magerlein, Barney J.; Hanze, A. R.; Jackson, Robert W.

doi:10.1021/ja01621a092

Cited by 43 publications

(8 citation statements)

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“…The enzymatically catalyzed reactions can replace several separate chemical steps in the synthesis of natural hormones and steroidal drugs such as corticosteroids and progestogens (reviewed in Fernandes et al, 2003). Specifically, the 11␣-hydroxyl derivatives of steroids represent commercially important intermediates in the production of contraceptive drugs (Jekkel et al, 1998) and synthetic glucocorticoid steroids used as anti-inflammatory, immunosuppressive, and anti-allergic drugs (Fernandes et al, 2003;Mahato and Garai, 1997) by offering access to the otherwise inaccessible site of the steroid molecule, which can then be chemically converted to the active form (Hogg et al, 1955).…”

Section: Introductionmentioning

confidence: 99%

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Petrič

Hakki

Bernhardt

et al. 2010

Journal of Biotechnology

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Section: Introductionmentioning

confidence: 99%

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Petrič

Hakki

Bernhardt

et al. 2010

Journal of Biotechnology

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“…[ ]3ß5 633°, [<*]d 160°; Xmax 238 µ (e 15,800); rmax 1810 and 778 cm-1 (cyclic carbonate). 18 Anal. Caled for 023 2807: C, 66.33; H, 6.78; CH30, 7.45.…”

Section: Methodsmentioning

confidence: 99%

“…8, 19721227 Utilizing this same approach, both possible epoxides 26a and 26b were prepared, the 20/3 epimer by reaction with alkali of the 20a-tosylate 25a [which was obtained from 21-acetoxy-l 1/3,17,20atrihydroxypregn-4-en-3-one (24a)14 with tosyl chloride in pyridine]; the 20a epimer by perbenzoic acid oxidation of the commercially available cis dienediol 28. 18 Lithium aluminum hydride reduction of either 26a or 26b followed by selective oxidation at C-3 with DDQ19 and column chromatography gave the 17,21-diol 29 in a yield of 40-50%. The compound was recovered either as a nicely crystalline solvate with methylene chloride or as its 21-acetate 30.…”

mentioning

confidence: 99%

Preparation and properties of .beta.-lactones from steroidal 17,20-dihydroxy-21-oic acids

Lewbart¹

1972

J. Org. Chem.

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The major neutral products from the reaction of the 17,20-dihydroxy-21-oic acids la and lb with acetic anhydride-pyridine are the 20-acetyl-21,17a-lactones 4a and 4b. A mechanism is presented to explain the controlling effect of configuration at C-20 on the extent of acetylation at C-17 us. C-21,C-17 cyclization. Spontaneous or thermal decarboxylation of 4a and 4b leads stereospecifically t o 6 and 7, the respective trans and cis enol acetates of the 17-aldehyde 8. Reaction of glycolic acids la and lb with ethyl chlorocarbonate-pyridine affords the 20-cathyl-21,17a-lactones 13a and 13b. Treatment of 1% with methanolic sodium hydroxide results both in cleavage of the p-lactone ring and formation of an epimeric mixture of the methyl ester 17,2O-cyclic carbonates 18a and 18b, in which the 20p epimer predominates. Similar treatment of p-lactone 13b gives the methyl ester cyclic carbonate without epimerization of C-20. Decarboxylation of 13a and 13b in refluxing methanol affords the trans and cis enol cathylates 16 and 17. Configurational assignments for both the latter compounds and the enol acetates 6 and 7 were made on the basis of their nmr spectral properties. Selective peracid oxidation of 16 and 17 furnished their respective 17,20-epoxides 20 and 21. Successive reaction of the epoxides with methanolic potassium bicarbonate and methanolic hydrogen chloride gave the 17a-hydroxy-20,20-dimethoxy derivative 22 as a common product. In order t o assess the contribution of the oxygen function at C-20 in 0-lactone formation, the 20-deoxy acid 34 was prepared. The essential role of the 20-acyl group is evident since treatment of 34 with either acylating reagent resulted in no appreciable formation of p-lactone. Instead, reaction with acetic anhydride-wridine movided the 17-acetate 36, and reaction with ethyl chlorocarbonate-pyridine gave the ethyl ester 37, pr&&mably by acylative decarboxylation.In an earlier communication2 we noted that reaction of the 17,20-dihydroxy-21-oic acids la and lb (Scheme I) with acetic anhydride-pyridine at room temperature affords the 17,20-diacetoxy-21-oic acids 2a and 2b as major products. We also recorded that a significant neutral fraction was generated in the reaction, but this material was not studied in detail at that time. Our more recent interest in cyclic derivatives of the pregnane side chain led us to reinvestigate this reaction. We have found, as originally postulated13 that the major neutral products are the 20-acetoxy-21,l7a-lactones 4a and 4b. This paper describes a general procedure for the direct preparation of 21,17a-lactones, some of the typical reactions which these compounds undergo, and a study of the structural features which favor plactone formation.Treatment of the 17,20a-dihydroxy-21-oic acid la with equal volumes of acetic anhydride and pyridine for 18 hr at 5" followed by careful partitioning of the reaction mixture between methylene chloride and cold, dilute sodium bicarbonate solution provided roughly equal amounts of acidic and neutral fractions. In accord wit...

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“…Subsequent debromination led to adrenosterone (25), which had also been obtained by other routes [30][31][32][33]. Following the method of Ruzicka [34] and Hogg [35], 25 was then converted into cortisone (28, R = H). Ethynylation of the former compound yielded 26, which on selective hydrogénation and treatment with phosphorus tribromide afforded the bromide 27.…”

Section: Adrenocortical Steroidsmentioning

confidence: 99%

Bc → BCD → Abcd

1974

Organic Chemistry: A Series of Monographs

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The ADRENAL HORMONES AND RELATED COMPOUNDS. I. A “DIRECT” SYNTHESIS OF HYDROCORTISONE ACETATE AND CORTISONE ACETATE FROM 11α-Hydroxyprogesterone

Cited by 43 publications

References 0 publications

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Preparation and properties of .beta.-lactones from steroidal 17,20-dihydroxy-21-oic acids

Bc → BCD → Abcd

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