Total assignment of <sup>1</sup>H and <sup>13</sup>C NMR spectra of 13α‐ and 13β‐estrone methyl ethers

Ciuffreda, Pierangela; Ferraboschi, Patrizia; Verza, Elisa; Manzocchi, Ada

doi:10.1002/mrc.891

Cited by 9 publications

(6 citation statements)

References 15 publications

(17 reference statements)

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“…All of the 1 H assignments in Table 1 are within 0.1 ppm of literature assignments by Kumar and Schneider 21 and Bischofberger et al 22 The 13 C assignments are also consistent (within an average deviation of 0.8 ppm) with literature values obtained for similar molecules and carbon environments using computational approaches 18,23 and 2D NMR, 24 and for E2 17 in acetone-d 6 (within an average deviation of 1.12 ppm). The 1 H and 13 C NMR assignments are the first reported for E2 in DMSO-d 6 .…”

Section: Discussionsupporting

confidence: 84%

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

et al. 2005

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The NMR-derived structure of estrogen (17b-estradiol, E2), the drug of choice for postmenopausal women, was compared with a recent literature crystal x-ray structure of Fab-bound E2.1 H and 13 C NMR spectra of E2 were acquired in DMSO-d 6 . Assignments were obtained from an analysis of DQF-COSY, TOCSY, HETCOR, HMQC and HMBC 2D NMR spectra. The 1 H and 13 C NMR assignments are the first reported for E2 in DMSO-d 6 . Two solution structures, S1 and S2, were obtained with molecular modeling using NOE constraints. S1 overlaps with the crystal structure for all rings. S2 shows prominent differences in the C-ring (C9-C11-C12-C13) segment, which deviates from a chair conformation, and excellent overlap in the A-, B-and D-rings of E2. The C-ring in S2 adopts a boat conformation as opposed to a chair conformation in the x-ray and S1 structures. The S2 structure is about 6• more twisted than the bound x-ray and S1 models. The S1, S2 and x-ray structures had ring bowing values of 10.1 ± 0.3, 11 ± 1 and 10.37• , respectively. Of the 100 solution conformers generated, 83 had S1 conformation and 17 had S2 conformation, with average internal energies of 112 ± 2 and 141 ± 2 kcal mol −1 , respectively. The 100 S1-and S2-derived conformers showed a r.m.s.d. of 0.72Å for all atoms. The x-ray, S1 and S2 C18 -O17 distances were 2.93, 2.92 ± 0.01 and 2.93 ± 0.01Å, respectively, and the O3 -O17 distances were 11.06, 11.18 ± 0.12, and 10.89 ± 0.05Å, respectively.

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Section: Discussionsupporting

confidence: 84%

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

et al. 2005

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“…The structure of ES, ES‐COOH, DSPE‐PEG 2000 ‐NH 2 and DSPE‐PEG 2000 ‐ES was confirmed by 1 H NMR spectra (Varian‐300 MHz NMR, Varian, USA) (Figures and ) . The typical 1 H NMR spectrum (300 MHz, CDCl 3 ) of DSPE‐PEG 2000 ‐ES showed peaks at δ 9.38 (m, 2H, 2 ×H‐Ar), 8.20 (m, 1H, H‐Ar) (Figure b).…”

Section: Resultssupporting

confidence: 89%

Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor – synthesis, physicochemical characterization and in-vitro evaluation

Hao

Yang

Sun

et al. 2017

Journal of Pharmacy and Pharmacology

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“…Bearing this in mind, and with a cascade of four COC bond-forming reactions involved in the conversion 55 3 56, each of the radical reactions proceeds with an average yield of Ϸ65%. Oxidation of the ring D methyl ether in 56 by using Jones' procedure next gave estrone methyl ether 57 which was then demethylated by using BBr 3 , leading to (Ϯ)-estrone 1, which had physical and spectroscopic properties identical with those described in the literature (62,63). In summary, two conceptually different radical-mediated cascade reactions from ortho-disubstituted aryl polyene and arylvinylcycloprane precursors, leading to the tricyclic B, C, and D rings of estranes in a single step, have been developed.…”

Section: Resultsmentioning

confidence: 83%

A total synthesis of estrone based on a novel cascade of radical cyclizations

Pattenden

González

McCulloch

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Two conceptually different and novel radical-mediated cascade reactions leading to a total synthesis of the steroid (؎)-estrone 1 and to a synthesis of 14-epiestrone 40 are described. Treatment of the iododienynone 23 with Bu3SnH͞2,2-azobis(isobutyronitrile) (AIBN) triggers a 13-endo-dig radical macrocyclization followed by two sequential radical transannulation reactions leading to the crystalline estrane 24 in 50% yield. The x-ray crystal structure of 24 established its trans, syn, stereochemistry. Transposition of the enone functionality in 24 next led to 38, which was then converted into 39 by reductive methylation. Deprotection of the methyl ether 39 finally gave 14-epiestone 40. When the substituted iodovinylcyclopropane 55 was treated similarly with Bu3SnH͞AIBN, the resulting radical center underwent a different sequence of cascade macrocyclization-transannulation reactions producing the trans, anti, trans estrane 56 in 12% overall yield. Oxidation of 56, using CrO 3-H2SO4 next led to the cyclopentanone 57, which, on deprotection using BBr3 gave (؎)-estrone 1. A number of alternative substituted iodopolyenynones and iodovinylcyclopropanes, i.e., 8a, 8b, 33, 49a, and 49b, underwent similar radical-mediated cascade cyclizations leading to other estranes, i.e., 21a, 21b, 35, and 50, and, in one case, to the 6,6,5,6-tetracycle 51, in variable overall yields. The structures and stereochemistries of several estranes were established by using x-ray crystal structure measurements in combination with analysis of their NMR spectroscopic data and correlation with literature precedent. Since the synthesis of the female sex hormone estrone 1 by Anner and Miescher in 1948 (1), and the syntheses of nonaromatic steroids, such as cortisone 2 and aldosterone 3 during the 1950s, a plethora of ingenious designs have been explored to synthesize members of the steroid family of natural products. Prominent among the methods that have been developed are those based on Diels-Alder reactions (2-12), transition metal-catalyzed cyclizations of enynes and triynes (13-16), and biogenetic-type electrophilic cyclizations of polyene precursors (17-21).Over the past 10 years, we (22-26) and others (27-38) have examined the scope of a variety of cascade radical-mediated processes to elaborate steroids and other polycyclic ring systems. Thus, we have already described an approach to steroids based on consecutive 6-endo-trig (ref. 39 and references therein) and sequential transannular (40) radical cyclizations from appropriate polyene selenyl ester precursors, illustrated in the conversions 4 3 5 and 6 3 7, respectively.We have now extended our studies and examined a different approach to estrone 1 and estranes, whereby the nonaromatic tricyclic B,C,D ring system is produced in a single step by radical-mediated macrocyclizations in tandem with consecutive transannulations from an appropriate ortho-disubstituted arylpolyene precursor.These approaches to estranes are captured in a retrosynthetic manner in Scheme 1. Thus, in one approach, we ha...

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Total assignment of ¹H and ¹³C NMR spectra of 13α‐ and 13β‐estrone methyl ethers

Abstract: The complete 1 H and 13 C chemical shift assignments of the 13a-epimer of estrone methyl ether and of estrone methyl ether itself were carried out, making use of oneand two-dimensional NMR techniques (1D HOHAHA, COSY, NOESY, TOCSY and HSQC).

Cited by 9 publications

References 15 publications

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor – synthesis, physicochemical characterization and in-vitro evaluation

A total synthesis of estrone based on a novel cascade of radical cyclizations

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Total assignment of 1H and 13C NMR spectra of 13α‐ and 13β‐estrone methyl ethers

Abstract: The complete 1 H and 13 C chemical shift assignments of the 13a-epimer of estrone methyl ether and of estrone methyl ether itself were carried out, making use of oneand two-dimensional NMR techniques (1D HOHAHA, COSY, NOESY, TOCSY and HSQC).

Cited by 9 publications

References 15 publications

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

Comparison of 17β-estradiol structures from x-ray diffraction and solution NMR

Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor – synthesis, physicochemical characterization and in-vitro evaluation

A total synthesis of estrone based on a novel cascade of radical cyclizations

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Total assignment of ¹H and ¹³C NMR spectra of 13α‐ and 13β‐estrone methyl ethers