The synthesis of 11β-alkyl-19-norsteroids: a novel class of potent steroid hormones—I

Baran, John S.; Langford, Donna D.; Laos, Ivar; Liang, Chia‐Jung

doi:10.1016/0040-4020(77)80300-1

Cited by 29 publications

(6 citation statements)

References 16 publications

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“…98 Quin and Marsi (5) l l a ful. Two of the 31P signals were quite similar (6 +37.6 and 6 +37.8) and probably could be assigned to the diastereoisomers of 11.…”

Section: -Phosphorinonesmentioning

confidence: 99%

“…The major isomer in the 4 : 1 mixture was assigned the trans structure (3b, 6 31P + 48.9), and the minor the cis structure (3a, 6 31P + 56. 5…”

Section: Synthesis Of M Ulticyclicmentioning

confidence: 99%

“…The solvent was evaporated in vacuo from the combined organic solutions to give a yellow oil. Chromatography (3% methanol in chloroform) followed by Kugelrohr distillation (76-81°C, 0.2 mm) afforded 9.9 g (68%) of 2 as a colorless oil consisting of a 45 : 55 mixture of dia- 16;H,9.39;found,C,62.14;H,4,5,6,7, …”

Section: 3-dimethyl-245677a-hexahydro-l (H)phosphindole 1 -Oximentioning

confidence: 99%

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Diketones from ozonolysis of fused 3‐phospholene oxides: Cyclizations to 3‐phosphorinone and to 1,4‐dihydro‐1,4‐azaphosphinine derivatives

Quin

Marsi

1990

Heteroatom Chemistry

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I -= Me or Ph) were prepared and ozonized at -78°C to give diketones in good yield. The intramolecular aldol condensation was performed on certain o f these ketones to give multicyclic 3-phosphorinone derivatives. I n some cases, double-bond rearrangement into the ring-f'usion position was encountered. The I-phenyl derivative in the benzophosphindole series could not be cyclized due to ready displacement of the P fragment from the tetralone system. The diketones reacted with ammonium acetate to give multicyclic derivatives of the 1,4-dihydro-l,4-azaphosphinine ring system. 1,2,3,4,5,6,7,8-0ctahydro-3-oxo-l -phenylphosphinoline I-oxide was used to demonstrate the value o f the bicyclic 3-phosphorinones as precursors of I-phosphadecalone derivatives. The carbonyl group was protected as the ethylene ketal and the double bond (as well as the benzene ring) was hydrogenated with ease. Hydrolysis gave the l-phospha-3decalone derivative. Reduction o f the same 3-phosphorinone with NaBH4 gave a mixture of diastereomeric alcohols.

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“…98 Quin and Marsi (5) l l a ful. Two of the 31P signals were quite similar (6 +37.6 and 6 +37.8) and probably could be assigned to the diastereoisomers of 11.…”

Section: -Phosphorinonesmentioning

confidence: 99%

“…The major isomer in the 4 : 1 mixture was assigned the trans structure (3b, 6 31P + 48.9), and the minor the cis structure (3a, 6 31P + 56. 5…”

Section: Synthesis Of M Ulticyclicmentioning

confidence: 99%

Section: 3-dimethyl-245677a-hexahydro-l (H)phosphindole 1 -Oximentioning

confidence: 99%

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Diketones from ozonolysis of fused 3‐phospholene oxides: Cyclizations to 3‐phosphorinone and to 1,4‐dihydro‐1,4‐azaphosphinine derivatives

Quin

Marsi

1990

Heteroatom Chemistry

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“…Many methods for introducing the 1,4-diene into the A-ring of steroids have been reported, for example, the use of selenium compounds, − DDQ (2,3-dichloro-5,6- dicyanobenzoquinone) as an oxidizing agent, , fermentation, − and bromination−dehydrobromination. − Among these, selenium compounds and DDQ are toxic and even gave the products in moderate yield. Fermentation needs a low substrate concentration and a very long reaction time, even though in the course of the production of corticosteroids, such as androstanedione and androstadienedione, from stigmasterol ( 6 ) and sitosterol ( 7 ), fermentation is the method for introducing alkenes into the A-ring.…”

Section: Introductionmentioning

confidence: 99%

Improved Synthetic Route to Dexamethasone Acetate from Tigogenin

Ohta

Zhang

Torihara

et al. 1997

Org. Process Res. Dev.

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In the synthesis of dexamethasone acetate from tigogenin, the introduction of the 17α-hydroxy-16α-methyl and the 1,4-diene moieties was improved. For the introduction of the 17α-hydroxy-16α-methyl moiety, the key step, epoxidation, was accomplished in high yield with peracetic acid in a buffer solution of sodium acetate and acetic acid (overall yield from 17-ene substrate to 17α-hydroxy-16α-methyl intermediate: 95.3%). Then the introduction of the 1,4-diene in the A-ring was greatly improved by bromination−dehydrobromination, in which dehydrobromination proceeded smoothly in a solvent system that was a mixture of DMF and 6% of water (82.6% isolated yield of 1,4-diene based on 3-oxo compound).

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“…We found that trituration (ether) of the epimeric mixture of 3-deprotected estrones effected a clean isomer separation, with the 1 1 p-ethyl epimer remaining as the insoluble component; chromatography has traditionally been employed to achieve this separation. 10 The receptor binding affinity (RBA), estimated non-specific binding (NSB) and their ratio, the binding selectivity index (BSl),ll for compounds 1-3, are shown in Table I, together with data for the corresponding estradiols. To assure attainment of equilibrium, the binding assay was conducted for 18 h at 25OC, rather than 4OC.12 The Ilp-ethyl substituent in estradiol and 2 elevates the RBA 9-11 fold; although the NSB also is increased, the BSI values are greatly elevated.…”

mentioning

confidence: 99%

Fluorine‐18 labeled 11β‐substituted estrogens: Synthesis, receptor binding, and comparative target tissue uptake studies

Pomper

Katzenellenbogen

Thomas

et al. 1989

Labelled Comp Radiopharmac

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Estrogens labeled with fluorine-I 8 show selective receptor-mediated uptake into estrogen target tissues,' and one agent, 1 6u-[1~F]fluoroestradiol ( l ) , has been used to image estrogen receptor-positive human breast tumors.2 In order to improve on the uptake characteristics of 1, we have examined the effect of 11 p-ethyl and 11 p-methoxy groups, as substituents at this site are known to substantially affect the binding behavior of estr0gens.3~4 The llp-methoxy substituent has been used by us5 and others6-8 to improve the target tissue uptake selectivity of estrogens labeled with the gamma emitters Br-77 and 1-125.1 1 p-Ethyl-1 6a-fluoroestradiol (2) and 1 1 p-methoxy-1 6a-fluoroestradiol (3) were ultimately produced by a facile fluoride ion (or [18F]fluoride ion displacement of the corresponding p-disposed trifluoromethanesulfonates (triflates), as previously described [Scheme 11.9 1-Dehydroadrenosterone serves as a common precursor to the 1 1 p-ethyland 1 1 p-methoxy-bis-triflates, which are prepared in thirteen and eleven steps, respectively, through modification of literature procedures.10 In the key step of the sequence to 2, the palladium-catalyzed hydrogenation (1 atm), a 2.5:1 preference for the desired llp-epimer was observed. We found that trituration (ether) of the epimeric mixture of 3-deprotected estrones effected a clean isomer separation, with the 1 1 p-ethyl epimer remaining as the insoluble component; chromatography has traditionally been employed to achieve this separation.10The receptor binding affinity (RBA), estimated non-specific binding (NSB) and their ratio, the binding selectivity index (BSl),ll for compounds 1-3, are shown in Table I, together with data for the corresponding estradiols. To assure attainment of equilibrium, the binding assay was conducted for 18 h at 25OC, rather than 4OC.12 The Ilp-ethyl substituent in estradiol and 2 elevates the RBA 9-11 fold; although the NSB also is increased, the BSI values are greatly elevated. The 1 lp-methoxy substituted in estradiol and 3 lowers the RBA, but the NSB is lowered to a greater extent, so that the BSI values are still higher than E2 and 1, respectively.

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The synthesis of 11β-alkyl-19-norsteroids: a novel class of potent steroid hormones—I

Cited by 29 publications

References 16 publications

Diketones from ozonolysis of fused 3‐phospholene oxides: Cyclizations to 3‐phosphorinone and to 1,4‐dihydro‐1,4‐azaphosphinine derivatives

Diketones from ozonolysis of fused 3‐phospholene oxides: Cyclizations to 3‐phosphorinone and to 1,4‐dihydro‐1,4‐azaphosphinine derivatives

Improved Synthetic Route to Dexamethasone Acetate from Tigogenin

Fluorine‐18 labeled 11β‐substituted estrogens: Synthesis, receptor binding, and comparative target tissue uptake studies

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