Preparation of sic 20-deoxysteroids in the 3.alpha.-hydroxy-5.beta.-pregnane series and their use in optical rotation studies

Lewbart, Marvin L.; Schneider, John J.

doi:10.1021/jo01269a002

Cited by 3 publications

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“…From Spontaneous Decarboxylation of 4b.-A crystalline sample of 20/3-acetoxy-3,ll-dioxopregn-4-ene-21,17a-lactone (46 mg) which had been stored at room temperature for several months had mp <100°and contained a more mobile artifact with the same Rf as the trans enol acetate 6. Silica gel chromatography furnished 5.6 mg of prisms from ether: mp 159.5-160.5°; [a]865 680°, [a]n 178°; Xmax 233 µ (<= 17,650); >w 1750, 1220 cm-1 (enolic acetoxyl);4 nmr 5 9.08 (s, 3, 18-CH3), 8.57 (s, 3, 19-CH3), 7.88 (s, 3, CH3CO), 7.05, 6.92 (d, 1, 12/3 ), 3.11 (t, 1,J = 2.0 Hz, 20 H).…”

Section: Methodsmentioning

confidence: 99%

“…17 from lb.-Sequential reaction of 17,20£-dihydroxy-3,lldioxopregn-4-en-21-oic acid with ethyl chlorocarbonate-pyridine and refluxing methanol as described in the preparation of 16 from la afforded 104 mg (37%) of enol cathylate 17 as prisms from methanol, mp 208-210°. 17, from 16.-To a solution of 20-carbethoxy-21-norpregna-4, irons-17(20)-diene-3,11-dione (90 mg, 0.24 mmol) in methylene chloride (5 ml) was added 80 mg (0.46 mmol) of m-chloroperbenzoic acid. After 3.5 hr at room temperature the solution was washed with dilute alkali and water and concentrated to dryness.…”

Section: Methodsmentioning

confidence: 99%

“…20a-Tosyloxy-21-acetoxy-l 1/3,17-dihydroxypregn-4-en-3-one (25a) from 24a.•-A solution of 110,17,2Oa, M. L. Lewbart, J. Org. Chem., 33, 1695(1968.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Lewbart¹

1972

J. Org. Chem.

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“…5 On the other hand, the key intermediate 5 could be prepared from its precursor 2, which can be easily prepared from commercially available pregnenolone acetate by applying the methods reported in the literature. 6,7 As outlined in Scheme 2, the synthesis of methyl spongoate started from the readily available 3,21-dihydroxypregnenane (2), which was prepared from pregnenolone acetate in five straightforward steps in 50% overall yield by following the procedures described in the literature. 6,7 Then 2 was first oxidized by the Jones reagent, 8 and the oxidation product was methylated with diazomethane to give compound 3 in 83% yield.…”

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confidence: 99%

“…6,7 As outlined in Scheme 2, the synthesis of methyl spongoate started from the readily available 3,21-dihydroxypregnenane (2), which was prepared from pregnenolone acetate in five straightforward steps in 50% overall yield by following the procedures described in the literature. 6,7 Then 2 was first oxidized by the Jones reagent, 8 and the oxidation product was methylated with diazomethane to give compound 3 in 83% yield. Subsequently, the 3-one derivative 3 was reduced with NaBH 4 9 in methanol at 4 °C to afford the corresponding alcohol 4 in 73% yield.…”

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confidence: 99%