Optical Rotatory Dispersion Studies. XVII.<sup>1</sup> Detection of Conformational Alterations. Effects of Alkyl Groups and Double Bonds in Polycyclic Systems<sup>2</sup>

Djerassi, Carl; Halpern, O.; Halpern, V.; Riniker, B.

doi:10.1021/ja01548a049

Cited by 73 publications

(19 citation statements)

References 7 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was then possible to examine the PMR spectrum for the presence of these isomers. The PMR spectrum of the product of the ozonolysis indicated that a mixture contained the epimeric ketones at (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) in the ratio of approximately 1:l. Two quartets were observed in this PMR spectrum: b 3.71 (J = 4.20 Hz) and 4.10 (J = 4.80 Hz). These quartets and the rest of the spectrum paralleled the chemical shifts and coupling constants reported previously for IV and V, respectively (1).…”

Section: Discussionmentioning

confidence: 99%

“…The bulky substituents surrounding the chloro group might force considerable distortion of ring E and, in effect, force the ring to be more planar. Djerassi et al (4) noted that some compounds that contain a gem-dimethyl grouping, as at C-20 in 111, in the vicinity of the chromophore showed inverted rotatory dispersion curves, attributed to conformational distortion of the system. Thus, the attacking methylene carbon could displace the chloro group either from above or below the plane of that ring.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structure of Lupeol and Its 19a-H-Isomer

Gearienx

Bauer

Klein

et al. 1975

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structure of Lupeol and Its 19a-H-Isomer

Gearienx

Bauer

Klein

et al. 1975

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Also, it is noted that all the calculated distances between the protons in this preferred conformation that show NOE correlations listed in Table 2 are less than 2.6 Å. To our knowledge, this is the most comprehensive NOE analysis of cycloartan-3-one derivatives, [8][9][10][11][12][13][14][15][16][17][18][19] and thus leading to the assignment of a preferred conformation of compound 2 in solution with the aid of advanced computational methods (B3LYP/6-31G*). This information indeed furnished the foundation for the theoretical calculation of its ECD spectrum.…”

mentioning

confidence: 88%

Capisterones A and B, which Enhance Fluconazole Activity in Saccharomyces cerevisiae, from the Marine Green Alga Penicillus capitatus

Jacob

Ding

et al. 2006

J. Nat. Prod.

View full text Add to dashboard Cite

A whole cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens, or cytotoxicity to several human cancer and non-cancerous cell lines (up to 35 μM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.The molecular mechanisms of antifungal drug resistance may involve a variety of factors such as mutation of target genes and decreased drug concentrations in the cells due to overexpression of efflux pumps. 1,2 In recent years, the rapid development of such drug resistance, particularly for azole antifungals, has highlighted the need for new strategies in antimycotic therapies. 1-5 Efflux pump inhibition has been considered as a promising approach in this regard. Two families of efflux pumps found in Candida albicans include the major facilitators (multidrug resistance, MDR) that are fueled by a proton gradient and the P-glycoprotein ABC transporters (Candida drug resistance, CDR) that require ATP hydrolysis for energy. Within each family, several subtypes have been discovered (i.e., CDR1, CDR2, MDR1). 1,2 We have established a whole cell-based assay using Saccharomyces cerevisiae strains that overexpress C. albicans CDR1 and MDR1 efflux pumps to screen for natural products that can reverse fluconazole resistance and may not be necessarily antifungal. 6In a continuing effort to search for new efflux inhibitors from natural sources, we have screened over 5000 marine extracts from the National Cancer Institute Open Repository. In the presence of a subinhibitory concentration of fluconazole, an extract of the tropical green alga Penicillus capitatus (Halimedaceae) that had an IC 50 value of 55 μg/mL against S. cerevisiae DSY 415 strain (overexpressing the CDR1 efflux pump) and an IC 50 value of < 6 μg/mL against S.

show abstract

“…coupling constants (12) aiid the 0.r.d. data (13) indicate that ring B is in the chair form except possibly in some derivatives containing bullty substituents a t the C6(P) position (12,14). The ring A conforination with Cz-up is favored since the alternative Cs-down structure brings the Cl(a) and Cll(a) hydrogen atoms within 1.7 A.…”

Section: A4-3-ketosteroids Containing 8:19-bridgesmentioning

confidence: 99%

Some Anomalous Carbonyl Stretching Frequencies in Steroid Infrared Spectra

Jones¹,

DiGiorgio²

1965

Can. J. Chem.

View full text Add to dashboard Cite

Ab~!ofmal C=O and C=C stretching freqi~encies in the infrared spectra of A'-3-ketosteroids containing a 19,s-lactone bridge are discussed in relation to possible conformational structures. The C=O stretching frequencies of 1,11,17-triketo-50-steroids and A2-1,11,17-triketo-~-steroids are reported. It is noted that the anomalous C=O stretching band position previously recorded for the 11-ketone in 11,17-diketosteroids is also observed in these triketones, but no additional perturbation results from the introduction of the 1-ketone group, in spite of its proximity to the carbonyl a t CII.The C=O stretching frequencies in the infrared spectra of ketosteroids and steroid esters in carbon disulfide, carbon tetrachloride, and chloroform solutions have been used extensively to characterize the type of carbonyl function. The spectra-structure correlations were summarized in 1954 (1) and again in 1958 (2). Subsequent investigations have confirmed the general applicability of these correlations to a wide range of steroids and derivatives.This paper deals with a few recently examined cases in which the infrared carbonyl frequencies exhibit unusual features. These involve the 19:8-bridged lactone structure I and the triltetones I I and I1 I. The spectra of A4-3-ketosteroids containing the 8: 19-epoxide bridge (IV), the 19:8-he~niacetal group (V), and the 19-methoxy-8: 19-epoxide bridge (VI) will also be discussed.

show abstract

Optical Rotatory Dispersion Studies. XVII.¹ Detection of Conformational Alterations. Effects of Alkyl Groups and Double Bonds in Polycyclic Systems²

Cited by 73 publications

References 7 publications

Structure of Lupeol and Its 19a-H-Isomer

Structure of Lupeol and Its 19a-H-Isomer

Capisterones A and B, which Enhance Fluconazole Activity in Saccharomyces cerevisiae, from the Marine Green Alga Penicillus capitatus

Some Anomalous Carbonyl Stretching Frequencies in Steroid Infrared Spectra

Contact Info

Product

Resources

About

Optical Rotatory Dispersion Studies. XVII.1 Detection of Conformational Alterations. Effects of Alkyl Groups and Double Bonds in Polycyclic Systems2

Cited by 73 publications

References 7 publications

Structure of Lupeol and Its 19a-H-Isomer

Structure of Lupeol and Its 19a-H-Isomer

Capisterones A and B, which Enhance Fluconazole Activity in Saccharomyces cerevisiae, from the Marine Green Alga Penicillus capitatus

Some Anomalous Carbonyl Stretching Frequencies in Steroid Infrared Spectra

Contact Info

Product

Resources

About

Optical Rotatory Dispersion Studies. XVII.¹ Detection of Conformational Alterations. Effects of Alkyl Groups and Double Bonds in Polycyclic Systems²